bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulation of mixed lymphocyte cultures and cytotoxic responses: evidence that T cells express SD but not LD antigens, whereas B cells express both
Authors: Simpson Elizabeth
Published: February 2007

By separating T and B cells from stimulator spleens it has been found that mixed lymphocyte response (MLR) and cytotoxic cells are generated in responder T cell populations by B but not by T stimulator cells in a wide variety of strain combinations.

It is suggested that MLR‐stimulating or LD antigens are expressed on B but not T cells, and that their presence is necessary in order to generate cototoxic responses to H‐2K and/or H‐2D (or SD) antigens which are present on both T and B cells. The finding that B cells and macrophages stimulate MLR is consistent with the hypothesis that Ia antigens, expressed on both these cell types but not on nylon column purified peripheral T cells, are the MLR‐stimulating or LD determinants.
The development of the thymus in the nude mouse
Authors: Owen J. J. T. , Jordan R. K. , Raff M. C.
Published: February 2007

The developing thymus of nude mouse embryos (derived from homozygous, nu/nu × nu/nu, matings) has been examined from 13 days' gestation onwards for the presence of large basophilic stem cells or their lymphoid progeny. No trace of either stem cells or lymphocytes has been found at any stage, indicating that from the earliest stages of thymic development lymphopoiesis is defective. However, histological evidence alone is not sufficient to rule out the possibility that small numbers of lymphocytes may be present in the nude thymus. Recent evidence that nude mice born of heterozygous (nu/+) females possess some T lymphocytes and “T lineage” cells is discussed in relation to these findings. A series of morphological changes have been defined within the epithelial component of the developing nude thymus, further analysis of which may help to determine the nature of the thymic defect.
Kinetics of the reactive cell clones after immunosuppression and induction of tolerance. II. Different recovery of 19 S and 7 S plaque‐forming cells after induction of tolerance
Authors: Botzenhardt U. , Lemmel E.‐M.
Published: February 2007

By the aid of two alkylating agents (cyclophosphamide (CP) and 036.5122, (Asta), applied after a single dose of antigen, tolerance to sheep red blood cells (SRBC), has been induced in NMRI mice. Duration and characteristics of recovery were followed by a second antigenic challenge at various time intervals and by determination of 19 S and 7 S plaque‐forming cells (PFC) 4 days later. During recovery from the tolerant state two phases of responsiveness could be differentiated: an early phase with no or markedly reduced numbers of total PFC, all of them being of the IgM type; a later phase with a steady increase in total PFC up to normal values, paralleled by an increase in the proportion of 7 S PFC finally reaching 90% of total PFC. In comparison with CP, recovery from tolerance induced by equitoxic doses of 5122 were delayed and modified. Even after 8 weeks, total PFC to SRBC were still depressed, and the ratio 19 S/7 S PFC resembled neither a typical primary nor secondary pattern.

It is concluded that CP‐mediated immunological tolerance is followed spontaneously by the establishment of a memory state. This observation, in agreement with findings of other authors, is interpreted as the expression of an established B cell memory compartment during the period of deficient T cell activity. The long‐lasting modification of specific responsiveness after 5122 indicates a profound disturbance of the potency to recover from the impact of this alkylating agent, the biological base of which is as yet unidentified.

It is suggested that observation of the characteristic features during the recovery phase from tolerance may help to clarify the nature of the defect in specific responsiveness.
Histocompatibility antigens and genetic control of the immune response in guinea pigs. II. Specific inhibition of antigen‐induced lymphocyte proliferation by anti‐receptor alloantisera
Authors: Geczy A. F. , Geczy C. L. , de Weck A. L.
Published: February 2007

The in vitro recognition of acetylsalicilyl ovalbumin, penicilloylated bovine IgG (BPO‐BGG) and the multichain copolymer poly‐L‐(Tyr, Glu)‐poly‐DL‐Ala‐poly‐L‐Lys [(T, G)‐A‐L] by primed (2 × 13) F1 cells could be markedly and specifically blocked by alloantisera directed against “receptors” (R) or recognition structures for these antigens. The antisera were raised against lymphoid cells from various F2 hybrid guinea pigs of (2 × 13) histocompatibility type in which responsiveness to low doses of acetylsalicylic acid anhydride, BPO‐BGG and (T, G)‐A‐L segregated independently of each other. One of the genes required for the expression of high responsiveness appears to be linked to the 13 MHC genes. The anti‐R antisera did not contain antibodies capable of interacting directly with the stimulating antigen since passage of the sera through antigen‐immunoadsorbent columns did not remove antibodies capable of suppressing in vitro recognition. Furthermore, the antisera did not appear to contain cytotoxic antibodies directed against specific antigen‐sensitive cells. The activity of the anti‐R sera was highly specific: their inhibitory activity could only be absorbed by lymphoid cells bearing the specific recognition structures for the appropriate antigen. Preliminary experiments yield no indication that the anti‐R antisera are specific for immunoglobulin idiotypes.
A general method for enumerating single cells secreting antigen: albumin‐secreting hepatocytes detected as plaque‐forming cells
Authors: Molinaro G. A. , Maron E. , Eby W. C. , Dray S.
Published: February 2007

Sheep erythrocytes, artificially coated with purified antibody specific for mouse serum albumin (anti‐MSA Ab‐E) were agglutinated and lysed by mouse serum albumin. Mouse liver cells, plated with anti‐MSA Ab‐E formed hemolytic plaques in a modified plaque in a modified plaque‐forming cell (PFC) assay. The same cells tested with anti‐MSA Ab‐E did not rosette in a modified immunocytoadhesion assay. Thus, liver cells secreted molecules (albumin) which were not detectable on the cell membrane. This PFC assay with Ab‐E is probably a general method for enumerating antigen‐secreting cells.
Immunological maturation in cell‐mediated immunity: progressive increase with time after sensitization in the ability of guinea pig peritoneal cells to discriminate between cross‐reacting determinants
Authors: Jokipii Liisa , Jokipii A. M. M. , Leskowitz S. , Kosunen T. U.
Published: February 2007

Guinea pigs were sensitized with the azobenzenearsonate (ABA) conjugates of the N‐acetyl derivatives of L‐tyrosine, L‐histidine and L‐tryptophan in complete Freund's adjuvant. After 4, 9 or 14 weeks, pertioneal cell migration inhibition was tested with each conjugate separately. The ABA‐specific reactivity was strongest at four weeks, but at that time there was no detectable immunological specificity beyond the ABA moiety. The ability to discriminate between the homologous and heterologous conjugates appeared between 4 and 9 weeks, and was also found at 14 weeks. Increasing fine specificity discrimination between cross‐reacting immunogenic determinants was interpreted as increasing average affinity of the recognition structures involved in peritoneal cell migration inhibition, i.e. the recognition structures of thymus‐dependent lymphocytes.
Dual pathway of B lymphocyte differentiation in vitro
Authors: Askonas Brigitte A. , Roelants G. E. , Mayor‐Withey Kathleen S. , Welstead Jacqueline L.
Published: February 2007

Direct visualization of the events resulting from LPS stimulation of mouse spleen cells in vitro was achieved by characterizing the cells during four days of culture for morphology, Ig and Θ surface markers and autoradiography after [3H] thymidine uptake. The changes observed were related to biochemical parameters such as incorporation of [3H] thymidine into DNA, Ig biosynthesis and secretion.

Two pathways of B lymphocyte differentiation were observed: a) the generation of a large number of small B lymphocytes with high density of surface Ig but no internal pool detectable by immunofluorescence, and b) the maturation of a very small proportion of cells with a large intracellular pool and the ability to secrete Ig. Both cell types arise from dividing blast cells, either physically separated or traced by pulse chase experiments with [3H] thymidine.

We discuss whether this duality is caused by the triggering of different B cell subpopulations at different developmental stages, preprogramed to one or the other pathway or whether the final direction of development depends on the microenvironment of individual dividing cells.
Modifications of the thymocyte membrane during redistribution of concanavalin A receptors
Authors: Wioland M. , Dormer M. , Neauport‐Sautes C.
Published: February 2007

The modifications of the thymocyte membrane which are induced by concanavalin A (Con A) were studied by means of the variation of electro phoretic mobility which the lectin induces on the cell. The electrophoretic mobility of thymocytes is increased when Con A is used under conditions expected to induce a cap formation and the subsequent endocytosis. This increase persists as long as the lectin is present in the medium and disappears as soon as the lectin is eliminated. The redistribution of the Con A receptors into spots and caps may partially explain this electrical modification. The ionized groups of the thymocyte membrane are drastically modified during these phenomena with: 1) a diminution by 61% in the density of the sialic carboxyl groups, 2) a decrease of 40% in the density of phosphate groups and of 60% in the density of amino groups, 3) a 20 times higher density of unidentified negatively charged groups.

The electrophoretic mobility of normal human blood lymphocytes is similarly increased by Con A. A marginal difference exists in the shape of the dose response curves obtained when normal and cancerous thymocytes react with increasing doses of Con A. No measurable electrical modification was observed during redistribution of H‐2 and Thy‐1.2 antigens on EL4 cells.

Some experiments suggest a possible correlation between the mitogenicity of the lectin and a measurable modification of the cell electrophoretic mobility.
Membrane Ig on human lymphocytes: rate of turnover of IgD and IgM on the surface of human tonsil cells
Authors: Ferrarini M. , Carte G. , Viale Giovanna , Durante Maria L. , Bargellesi A.
Published: February 2007

The turnover of IgM and IgD molecules present on the membrane of human tonsil cells has been studied using immunofluorescence and peroxidase‐catalyzed membrane radioiodination. With the first of the two techniques cells were treated with pronase to remove membrane immunoglobulin (mIg), placed in culture and stained at intervals to check the reappearance of membrane IgD and IgM on the cell membrane. These experiments showed that membrane IgD (in contrast to membrane IgM) are extremely susceptible to proteolysis. Furthermore, cells treated with a concentration of pronase found to be optimal to remove membrane IgM failed to re‐express membrane IgD in vitro. The large majority of tonsil lymphocytes has both membrane IgM and IgD. Due to the different behavior of re‐appearance of the two membrane molecules after treatment with pronase, it was not possible to obtain the simultaneous re‐expression of membrane IgM and IgD by the cells “stripped” with pronase. However, the two molecules were re‐ex‐pressed in vitro by the cells treated with different pronase concentrations with a similar timing, i.e. 50 % or more of the cells re‐expressed membrane IgD and IgM after 8 h in culture. 131I‐radioiodinated membrane IgD and IgM were also released from the cell surface with a. similar timing, the half‐life of permanence on the cell membrane being about 4 h for both molecules. These findings thus indicate that IgM and IgD molecules have a similar turnover and that a cell is capable of placing two different Ig molecules at a time on its surface.
Lymphocyte proliferation in vitro induced by soluble protein antigens. II. Cellular requirements
Authors: Hertel‐Wulff Birgit , Rubin B.
Published: February 2007

Immune guinea pig lymph node cells were fractionated on Ig anti‐Ig or HSA anti‐HSA affinity columns or on plastic surface in medium containing carbonyl iron. These techniques selectively removed B lymphocytes, K lymphocytes or adherent cells. The residual cells (Fc receptor‐negative T lymphocytes) responded to soluble antigen in vitro in the same way or even better compared with nonfractionated cells. In addition, there was no indication that antigen‐antibody complexes were superior to antigen in triggering lymph node cells or purified lymph node T lymphocytes into DNA synthesis. The results obtained suggested that memory T lymphocytes can be stimulated by antigen autonomously.
Genetic control of the immune response: ability of antigens of defined amino acid sequence to be recognized by the Ir‐1 gene system
Authors: Seaver Sally S. , Brown A. , Hämmerling G. , McDevitt H. O.
Published: February 2007

Mice were injected with a series of (T, G)‐A–L [poly (L Tyr, L Glu)‐poly(DL Ala)– poly (L Lys)]‐like compounds with side chains of homogeneous sequences: T‐A–L, GT‐A–L, GGT‐A–L, and TG‐A–L. T‐A–L was not immunogenic. However, T‐A–L was able to bind antibodies to (T, G)‐A–L 509, and this binding could not be blocked by A–L. When complexed with bovine serum albumin, T‐A–L, was immunogenic in both responder and nonresponder strains of mice. GT‐A–L and GGT‐A–L were both immunogenic and elicited the characteristic responder‐nonresponder difference induced by (T, G)‐A–L. TG‐A–L was also immunogenic, but there was considerable overlap in the response of responder and nonresponder strains. On the average, responder mouse serum had a slightly higher antigen‐binding capacity than nonresponder mouse serum. In contrast to antibodies against GGT‐A–L, antibodies against TG‐A–L bound heterologous antigens poorly.

These data, along with the results of other investigators, are consistent with the hypothesis that there are multiple Ir‐1 genes which recognize different sequences. The specificity of the Ir‐1 genes is extraordinary. The polypeptides TG‐A–L, TGTG‐A–L and GTTG‐A–L do not appear to be recognized by these genes.
Nature of cells binding anti‐IgE in rats immunized with Nippostrongylus brasiliensis: IgE synthesis in regional nodes and concentration in mucosal mast cells
Authors: Mayrhofer G. , Gowans J. L. , Bazin H.
Published: February 2007

The possibility that IgE is a secretory immunoglobulin has been examined by studying the tissue and cellular localization of IgE in rats infested with the enteric parasite, Nippostrongylus brasiliensis. The lamina propria of the small intestine and the colonic and pulmonary mucosal surfaces contained numerous anti‐IgE‐binding cells, but these were shown to be mast cells and not plasma cells. The major site of IgE synthesis was the regional lymph node of the small intestine, the mesenteric node, which contained large numbers of IgE‐secreting plasma cells. Smaller numbers of IgE‐secreting plasma cells were also found in the axillary node, which drained the site of larvae injection. Peyer's patches, the intrapulmonary bronchial lymphoid tissue and the spleen contained few, if any, IgE‐secreting plasma cells. The significance of the IgE which was readily demonstrated in germinal centers of the mesenteric lymph nodes, the Peyer's patches and the axillary lymph nodes, is not known. In contrast to the infested animals, the lymphoid organs of normal rats rarely contained any IgE‐containing cells. An unexpected observation was that mast cells in mucosal organs appear to contain intracellular IgE, differing in this respect from connective tissue mast cells. Mast cells lying between epithelial cells, the “globule leukocytes”, also appear to contain intracellular IgE, and it is suggested that such cells may be responsible for the presence of IgE in exocrine secretions. This study does not support the suggestion that IgE is a secretory immunoglobulin with a Physiology analogous to that of IgA.
Deletion of hinge region of human myeloma lgG1 molecule (protein LEC) associated with nonexpression of G1m(3) and Km(1,2) allotypes. A possible genetic explanation at the DNA level
Authors: Rivat C. , Rivat Liliane , Ropartz C. , Schiff Claudine , Fougereau M.
Published: February 2007

In this paper we report the structural basis for the nonexpression of G1m(3) and Km(1, 2) allotypes in an IgG1 (K) human myeloma protein (protein LEC). Heavy and light chains spontaneously dissociate in sodium dodecyl sulfate polyacrylamide gels. Light chains appear to be covalently S‐S bonded. Analysis of cysteine‐containing peptides shows that the heavy chain of the IgG protein LEC has a deletion of residues 21 6‐230, thus encompassing the entire hinge region. An arginine residue, characteristic of the G1m(3) marker is present at position 214. An alanine at position 153 and a leucine at position 191 of the light chain, characteristic of the Km (1, 2) allotypes, are present. It is likely that the double Km and Gm lack of expression is the result of the deletion. The genetic implications of the sequence of this protein are discussed.
Immunological properties of murine thymus‐dependent lymphocyte surface glycoproteins
Authors: Trowbridge I. S. , Mazauskas Catherine
Published: February 2007

The immunological properties of two murine thymus‐dependent (T) lymphocyte surface glycoproteins, T200 and T25, were investigated. T200 is a lymphocyte‐specific antigen with a high degree of species specificity. It shares antigenic determinants with molecules present on thymus‐independent (B) lymphocytes.

T25 has antigenic determinants which cross‐react with antigens on mouse brain, rat thymocytes and rat brain. An antiserum against a purified rat brain glycoprotein which carries Thy‐1.1 reacts with T25. Absorption of this antiserum with BALB/c thymocytes or brain homogenate produces a Thy‐1.1 ‐specific serum which reacts with T25 from AKR/J thymocytes but not with T25 from AKR/Cum thymocytes. These results confirm that T25 is the molecule on the surface of mouse T cells which carries the Thy‐1 antigen. T25 also carries antigenic determinants, recognized by anti‐thymocyte serum (ATS), which were found on secondary mouse embryo fibroblasts and untransformed fibroblast cell lines but which were not detected on fibroblast cell lines transformed with murine sarcoma virus (MSV) or with Simian virus 40 (SV40).

A third T lymphocyte‐specific antigen with an apparent mol. wt. of 35 000 Daltons, that is recognized by ATS and is expressed on thymocytes and spleen cells, was detected. In contrast to T25 this molecule is not present on brain nor on BW5147, a T cell lymphoma.
HLA‐B specificities and w4, w6 specificities are on the same polypeptide
Authors: Ayres Janet , Cresswell P.
Published: February 2007

The human alloantigenic specificities w4 and w6, which are products of a diallelic system genetically associated with the HLA‐B locus, have been solubilized by papain digestion of membranes from the lymphoblastoid cell line, RPMI 4265. The w4 and w6 specificities copurified with the HLA‐B locus products, HLA‐B7 and HLA‐B12. Sequential immunoprecipitation experiments were performed using alloantisera to HLA‐B7, HLA‐B12, w4 and w6, and a purified HLA‐B7, B12, w4, w6 antigen pool labeled with 125I‐Bolton‐Hunter reagent. These experiments demonstrated directly that HLA‐B7 and w6, which are genetically associated with each other, are different antigenic determinants on the same molecule, while HLA‐B12 and w4, also genetically associated, are distinct antigenic determinants on a second molecule. Arguments are presented which suggest that the HLA‐B determinants and w4, w6 determinants are in fact on the same polypeptide, and the genetic implications of the findings are discussed.
Malarial immunodepression in vitro: adherent spleen cells are functionally defective as accessory cells in the response to horse erythrocytes
Authors: Warren H. S. , Weidanz W. P.
Published: February 2007

The basis for the depressed response of malarial infected mice to horse red blood cells (HRBC) has been studied in vitro. Results presented show that the adherent spleen cells from infected mice (a) are defective in their ability to allow nonadherent spleen cells of both normal and infected mice to respond to HRBC whereas a response does occur with adherent spleen cells from normal mice (b) do not suppress the response of unfractionated spleen cells from normal mice to HRBC (c) contain phagocytic cells as measured by the uptake of neutral red in numbers which are of the same order of magnitude as in adherent spleen cells from normal mice, but which are unable to take up HRBC. We conclude that a splenic adherent cell, probably the macrophage, is functionally defective as an accessory cell in the response to HRBC of mice infected with Plasmodium berghei yoelii.
Antigenic specificity of the cytolytic T lymphocyte (CTL) response to murine sarcoma virus‐induced tumors. I. Preferential reactivity of in vitro generated secondary CTL with syngeneic tumor cells
Authors: Plats F. , Cerottini J.‐C. , Jongeneel V. , Brunnera K. T.
Published: February 2007

Incubation of spleen cells from mice having rejected a Moloney sarcoma virus (MSV)‐induced tumor with syngeneic irradiated lymphoma or sarcoma cells bearing MSV‐associated antigens in secondary mixed leukocyte‐tumor cell cultures (MLTC) resulted in the generation of highly active cytolytic T lymphocytes (CTL) specifically directed against syngeneic target cells bearing MSV‐associated antigens. When MSV‐immune spleen cells from C57BL/6 (H‐2b) and BALB/c (H‐2d) mice were compared with respect to their ability to generate CTL in syngeneic secondary MLTC, it was found that both lymphoid cell populations were equally able to mount an anamnestic CTL response to MSV‐associated antigens as assessed by a short‐term 51Cr release assay. However, quantitative analysis of the activity of both CTL populations on either H‐2b or H‐2d tumor cells indicated that target cells sharing the same major histocompatibility complex (MHC) as the effector cells were lysed 10‐ to 100‐fold more efficiently than allogeneic target cells. As suggested by the results of inhibition experiments using mixtures of 51Cr‐labeled and unlabeled target cells, preferential lysis of syngeneic versus allogeneic tumor cells might be related to the establishment of effective adhesions between the former and CTL.

Direct evidence for the role of MHC in determining the antigenic specificity of CTL directed against MSV‐associated antigens was provided by results obtained using MSV‐immune spleen cells from congenic resistant mice. Furthermore, studies of the response of F1 (H‐2b/d) hybrid mice showed that stimulation of immune spleen cells with tumor cells from one parental strain or the other in secondary MLTC resulted in the generation of CTL capable of lysing tumor target cells of the same parental strain as the stimulating cells, but not of the other. The results thus suggested the presence of two sets of CTL precursor cells in F1 MSV‐immune spleens, each set responding exclusively to tumor antigens associated with only one of the two parental phenotypes.
Lack of effect of thymectomy on spontaneous recovery from tolerance to levan
Authors: Howard J. G. , Courtenay Barbara M. , Hale Christine
Published: February 2007

Adult CBA mice were made tolerant with 1 mg levan and tested subsequently for spontaneous recovery by plaque‐forming cell assay in response to immunizing challenge. Weakening of tolerance was first detectable only after 100 days, while return to full normal responsiveness required 400 days. Thymectomy 2 weeks prior to tolerization neither retarded nor diminished the recovery process. Loss of tolerance which had been induced by 1 mg dextran B512 was much slower in onset (> 250 days), yet not delayed by thymectomy (full recovery was not followed).

These findings in relation to other considerations imply that associative recognition by T cells is not required for B cell responses to these “thymus‐independent” antigens.
Immunoglobulin‐like messenger RNA in a mouse T cell lymphoma
Authors: Babbitts T. H. , Forster A. , Smith M. , Gillam S.
Published: February 2007

RNA‐driven complementary DNA (cDNA) hybridization experiments have been carried out in order to detect complementary sequences in RNA prepared from a mouse T cell lymphoma line (EL4). In conditions where efficient hybridization of L‐chain cDNA with homologous P3 myeloma mRNA was observed, poor hybridization was observed with EL4 mRNA unless a low criterion of hybrid formation was employed (i.e. hydroxyapatite fractionation). The hybrid formed between EL4 mRNA and L‐chain cDNA was found to melt about 5 °C below the homologous hybrid indicating that the sequence detected in EL4 mRNA is similar but not identical with the P3 mRNA sequence. However, a similar sequence was detectable in a Cλ‐producing myeloma cell line but in this line the concentration of the sequence was found to be an order of magnitude lower than in EL4 cells.
Induction and characterization of “autologous” anti‐idiotypic antibodies
Authors: Cosenza H. , Augustin A. , Julius M. H.
Published: February 2007

Upon immunization with phosphorylcholine (PC), conventional BALB/c mice produce anti‐PC antibodies bearing predominantly the idiotype characteristic of the BALB/c PC‐binding myeloma protein TEPC 15 (T1 5). To investigate whether BALB/c mice are able to produce antibodies to the autologous T15 idiotype, conventional (T1 5‐positive) and neonatally suppressed (T1 5‐negative) BALB/c mice were immunized with purified T15 myeloma protein. Both groups of mice produced IgG antibodies specific for the T1 5 idiotype. However, anti‐T 15 antibodies were more readily induced in neonatally suppressed mice which in turn produced higher anti‐T15 titers than conventional mice. Such “autologous” anti‐T 15 antibodies are able to (a) change the idiotypic pattern of the anti‐PC response of conventional BALB/c mice in situ and, (b) inhibit the induction of an anti‐PC response in vitro by spleen cells from T15‐positive but not T15‐negative BALB/c mice. Thus, BALB/c mice are capable of producing anti‐T 15 antibodies upon immunization with an isologous myeloma protein which bears the autologous T1 5 idiotype. We suggest that idiotypes should not be strictly considered as “self‐antigens” since the dramatic increase in their concentration, subsequent to antigen stimulation, might confer upon them immunogenic properties not shared by self‐antigens.
Reducèd in vitro response to concanavalin A and lipopolysaccharide in senescent mice: a function of reduced number of responding cells
Authors: Abraham Carmella , Tal Y. , Gershon Harriet
Published: February 2007

Studies of the cell cycle of cells responding to Con A and to LPS from 12 and 28‐month‐old mice demonstrate that the generation time of individual proliferating cells does not alter with age. Nor does it differ for the B cells responding to LPS or the T cells responding to Con A. These studies also demonstrate that the proliferating cells from senescent mice are equally capable of repeated cell divisions as are the cells from the 1‐year‐old adult mouse. It is concluded that the defect in senescent mice which leads to a reduced in vitro response to the polyclonal mitogens LPS and Con A is a reduction in the number of responding cells and not an alteration in the capacity of those cells which do respond to divide.

The proliferative capacity of spleen cells from C57BL/6J female mice of various ages (3‐28 months) to the polyclonal mitogens concanavalin A (ConA) and lipopolysaccharide (LPS) was examined. It was found that both the T and B cell population of the spleen demonstrate an age‐related decrease in their capacity to respond in vitro. Peak responses to both mitogens occurs at about 1 year of age. This age‐related reduction in response is expressed in the degree of incorporation of [3H]thymidine into DNA, the total number of cells generated in vitro, the number of labeled cells per culture and the number of blast cells per culture. The day of peak response in vitro does not change with age.
Suppressor cell induction in vitro
Authors: Kontiainen Sirkka , Feldmann Marc
Published: February 2007

Antigen‐specific suppressor T cells induced in vitro release, after a further period of culture in vitro with antigen factors into the supernatant which have suppressor activity. These suppressor factors (SF) have the same antigen specificity as the suppressor cells (SC). SF only works on the early phase of thymus‐dependent responses in cultures. SF inhibits thymusdependent IgM, but not thymusindependent IgM responses in vitro. SF is destroyed by proteolytic enzymes, and inactivated at 80°C for 30 min. The release of SF from SC is dependent on the presence of antigen and metabo‐lically active cells.
Characterization of B cell subpopulations by velocity sedimentation, surface la antigens and immune function
Authors: Press Joan L. , Strober S. , Klinman N. R.
Published: February 2007

An in vitro splenic focus assay for B cell cloning was used to analyze the responses of primary and secondary B cells obtained after fractionation on (1 × g) velocity sedimentation gradients. When nonimmune adult bone marrow cells are fractionated, the small cell (slowly sedimenting) fraction contains the majority of primary B cells specific for the 2,4‐dinitrophenyl determinant (DNP). When nonimmune adult spleen cells are fractionated, all of the cell fractions contain B cells specific for DNP or for fluorescein (FL), and the large and medium cell fractions contain approximately 50 % of the activity. There is a differential expression of IgM vs. IgG1 anti‐hapten monoclonal antibody, in that the majority of primary splenic B cells which give rise to clones producing only IgM antibody are found predominantly in the large and medium cell fractions. All of the cell fractions contain B cells which can generate clones producing both IgM and IgG1, or only IgG1 antibody. Ia‐“negative” B cells which give rise to clones producing only IgM antibody are found in the large and medium cell fractions, whereas all the cell fractions contain la‐positive B cells. When secondary spleen cells are fractionated, all of the cell fractions contain secondary B cell activity. The large and medium cell fractions contain half of the DNP‐specific secondary B cells, whereas the medium and small cell fractions contain more secondary B cells specific for FL or hemocyanin. The large and medium cell fractions of secondary spleen cells are not enriched for B cells giving rise to clones producing only IgM antibody.
Increase in T cell mitogen responsiveness in rat thymocytes by thymic epithelial culture supernatant
Authors: Kruisbeek Ada M. , Kröse Tonny C. J. M. , Zijlstra Jelly J.
Published: February 2007

Supernatants from rat thymic epithelial cultures (TES) increased [14C]thymidine incorporation into rat thymocytes stimulated with phytohemagglutinin (PHA) or concanavalin A, whereas supernatants from nonthymic control tissue cultures had no effect. It was demonstrated that the increased mitogen responsiveness was at least partially due to an increase in the number of responsive cells. Furthermore, our data suggest that the target cell for TES resides among the cortisone‐sensitive population of thymocytes. The continuous presence of TES provided the best conditions for enhancement of mitogen stimulation. The addition of TES had very little effect on mitogen‐stimulated spleen and lymph node lymphocyte cultures.

The data suggest that, in the presence of TES, a cortisone‐sensitive, PHA‐nonre‐sponsive subpopulation of rat thymocytes is induced to respond to PHA.
Mechanisms of B cell tolerance
Authors: Abbas A. K. , Klaus G. G. B. , Mcelroy P. J.
Published: February 2007

Exposure of 2, 4‐dinitrophenyl (DNP)‐hemocyanin‐primed spleen cells to DNP‐conjugated pneumococcal polysaccharide (DNP‐S3) in vivo or in vitro renders such cells unresponsive to DNP‐hemocyanin challenge following adoptive transfer. The unresponsiveness is hapten‐specific, independent of the presence of T cells and adherent cells, and not due to either toxic effect of S3 or carry‐over of tolerogenic amounts of cell‐bound DNP‐S3, and thus presumably represents a model of B cell tolerance. The degree of suppression induced depends upon the dose of the tolerogen and most strikingly on the duration of exposure of cells to the tolerogen. Thus 2 to 6 h exposure to DNP‐S3 has an insignificant effect on anti‐DNP responses, while 24 and 48 h exposures in vitro and in vivo are highly suppressive. Such a dynamic process of tolerance induction suggests a “multiple hit” phenomenon, implying the generation of suppressive signals by repeated cycles of tolerogen‐receptor interactions. The process can be interrupted by removal of extracellular DNP‐S3, although this does not reverse the unresponsiveness that has already been induced.
Prevention of tolerance induction to a thymus‐dependent antigen by poly (A) poly (U)‐induced thymocyte fluid
Authors: Fessia Sandra L. , Kong Y.M. , Bick P.H. , Johnson A.G.
Published: February 2007

The prevention of tolerance induction by a thymus‐derived (T) cell factor induced with a complex of synthetic polyadenylic‐polyuridylic acid (poly (A) · poly(U)) was studied. The soluble factor(s) was obtained by exposing mouse thymocytes to poly (A) · poly(U) for 10 min, washing and culturing them for an additional 6 h in serum‐free medium. This factor in the supernatant fluid of the culture, termed AUSF, prevented tolerance induction to soluble bovine IgG (sBGG) in vivo when administered to mice 3 h after tolerogen. The effect was manifested by a marked increase in rosette formation by spleen cells and hemagglutinin titers to BGG compared with mice given sBGG only. And, as shown previously, AUSF enhanced plaque formation to red blood cells (RBC) by spleen cells in vitro. Supernatant fluids from untreated, but cultured, thymocytes showed some activity, but much less than those from poly (A) poly(U)‐stimulated cultures. AUSF was found to function across histocompatibility differences since preparations from both syngeneic and allogeneic mice were effective in interfering with tolerance induction. The data suggest that poly(A) · poly(U) prevents tolerance induction to a thymus‐dependent antigen by the early release of a T cell factor before antigen‐reactive T cells have become tolerant.
Specificity of H‐2‐linked Ir gene control in mice: recognition of defined sequence analogs of (T, G)‐A–L
Authors: Rüde E. , Günther E. , Meyer‐Delius Margot , Liehl E.
Published: February 2007

In order to study the specificity of H‐linked Ir gene control in more detail the polypeptide poly(LTyr, LGlu>poly(DLAla)–poly(LLys) ((T, G)‐A‐L) was modified by replacing the (T, G) copolymers by various defined tyrosine‐containing oligopeptides. It was found that the antibody response to all of the analogs of (T, G)‐A–L tested was influenced to some extent by H‐2‐linked Ir gene(s), the response pattern being concordant with that of (T, G)‐A–L. Some of the antigens carrying structurally and serologically distinct oligopeptides were as efficient with respect to high/low responder discrimination as (T, G)‐A–L, others including the core polypeptide A‐L itself were weakly immunogenic and gave only a small high/low responder split.

Certain experimental data indicate that in addition to the tyrosine peptides the poly‐DL‐alanine side chains may play an important role for the recognition of these polypeptides. The possibility that the common response pattern could be due to an Ir gene specific mainly for the DL‐alanine peptides is discussed. Specificity of genetic control would then be relatively independent of the serological specificity of the tyrosine peptides. On the other hand, recognition of the analogs and of (T, G)‐A–L could be controlled by separate but closely linked Ir genes specific for each of the terminal peptide determinants which probably include the adjacent alanine residues.

Genetic factors outside the H‐2 complex have in addition to the H‐linked Ir genes been found to exert a strong influence on the antibody response to some of the analogs of (T, G)‐A–L.
Idiotypic analysis of the response of C57BL/6 mice to the (4‐hydroxy‐3‐nitrophenyl)acetyl group
Authors: Jack R.S. , Imanishi‐Kari Thereza , Rajewsky K.
Published: February 2007

Strain C57BL/6 mice produce a highly restricted primary response to the (4‐hydroxy‐3‐nitrophenyl)acetyl (NP) group. This response is composed of molecules having μ or γ1 heavy chains and light chains of the λ type. A guinea pig anti‐idiotype was raised to the purified C57BL/6 primary anti‐NP immunoglobulin. After suitable absorption, this anti‐idiotype was shown to detect markers present on the primary anti‐NP immunoglobulin only of those strains which express the Ig‐lb allotype. Breeding experiments demonstrated that the marker segregated with the heavy chain linkage group.
Molecular structure of human histocompatibility antigens: the HLA‐C series
Authors: Snary D. , Barnstable C.J. , Bodmer W.F. , Crumpton M.J.
Published: February 2007

The HLA‐CW2 antigen of the B lymphoblastoid cell line BRI 8 is structurally homologous to the HLA‐A and B antigens as judged by various criteria. Each antigen comprised a glycosylated polypeptide of 43 000 molecular weight that is noncovalently associated with β2–microglobulin (β2 m). Some small differences in molecular parameters were, however, revealed. Thus, the deoxycholate‐solubilized HLA‐CW2 antigen sedimented at the same rate as the HLA‐A antigens but at a slightly faster rate than the HLA‐B antigens. This variation is apparently due to different amounts of bound deoxy‐cholate. Also, whereas essentially all of the HLA‐A and B antigens and about half of the HLA‐CW2 antigen were adsorbed Strongly by Lens culinaris lectin‐Sepharose, the remaining HLA‐CW2 antigen was bound much more weakly and did not require sugar for elution. This difference reflects some structural heterogeneity in the carbohydrate moiety of the HLA‐CW2 antigen. The results of various studies suggest that the HLA‐CW2 antigen is expressed to a lower extent than the HLA‐A or B antigens and that essentially all of the β2 m of the BRI 8 plasma membrane is associated with the HLA‐A, B and C alloantigenic polypeptides.
Mouse bone marrow‐cultured macrophage as indicator cells for mouse and human migration inhibitory factor (MIF)
Authors: Lohmann‐Matthes Marie‐Luise , Domzig W. , Meerpohl H. ‐G.
Published: February 2007

Macrophages cultured from mouse bone marrow served as excellent indicator cells for mouse as well as for human migration inhibitory factor (MIF) preparations. The tests were performed in the capillary system and showed high reproducibility. Using mouse or human MIF‐containing supernatants, we found an inhibition of 53 % compared with the controls. Similar results were obtained if concanavalin A‐stimulated human peripheral blood lymphocytes were mixed with mouse test macrophages in a ratio of 1:5 or 1:10.
Regulation of delayed‐type hypersensitivity I. T suppressor cells for delayed‐type hypersensitivity to sheep erythrocytes in mice
Authors: Liew F.Y.
Published: February 2007

Mice injected with 1 x 108 sheep red blood cells (SRBC) into the footpad showed high levels of delayed‐type hypersensitivity (DTH) to SRBC 4‐8 days after the injection. In contrast, mice injected intravenously with 1 x 109 SRBC were unresponsive to DTH induction through 1 x 108 SRBC injected into the footpad. This suppression of DTH was maintained for at least 6 weeks and was transferable by spleen, lymph node and thymus cells to normal syngeneic recipients. Bone marrow cells, on the other hand, did not contain the suppressor cells. The suppression of DTH was antigen‐specific in that DTH to chicken red blood cells and contact sensitivity to 2,4‐dinitrofluorobenzene was not affected. The suppressor cells were theta‐positive and Ig‐negative. They appeared in the spleen in optimum number 3–4 days after induction. The suppressor cells affected both the induction and manifestation of DTH. The presence of suppressor and effector cells for DTH inducible by different routes of antigenic presentation reflects the dynamic balance in the regulation of DTH.
Thymocyte subpopulations in young and adult mice II. Study of steroid‐resistant populations by means of a specific heteroantiserum
Authors: Papiernik Martine , Bach J.F.
Published: February 2007

Mouse steroid‐resistant (Sr) cells of the thymus have been studied by means of a specific heteroantiserum. This antiserum was obtained in the rabbit after immunization with Sr thymocytes followed by absorption with high density cells isolated on a Ficoll density gradient shown to include a majority of steroid‐sensitive (Ss) cells. Antigens defined by this antiserum were found on Sr thymocytes and on a significant portion of spleen and lymph node cells, but not on Ss cortical thymocytes. Cells sensitive to this antiserum appear early in the thymus (by day 15 of gestation) at the same time as Ss cells. These results suggest (a) the existence of an autonomous Sr cell line, with its own antigenic markers appearing early in ontogeny (at the same time as Ss cells), and showing wide heterogeneity in density, possibly linked to variable degrees in maturation, and (b) the medullary origin or some peripheral lymphocytes in lymph node and spleen cells that share antigenic markers with Sr thymocytes.
Split unresponsiveness to the trinitrophenyl determinant I. Manoeuvers which suppress either humoral or cell‐mediated immune responses
Authors: Ptak W. , Różycka Danuta
Published: February 2007

2,4,6‐Trinitrobenzene sulfonic acid (TNBS) injected intravenously (i.v.) makes mice fully tolerant to the trinitrophenyl (TNP) determinant. Administration of in vitro TNP‐labeled syngeneic erythrocytes or thymocytes renders mice unable to develop contact sensitivity to picryl chloride, while the humoral anti‐TNP responses seem to be unaffected. The reverse was found after pre‐treatment of mice with TNP‐labeled isologous IgG (MGG) since only anti‐TNP antibody responses, but not contact sensitivity to picryl chloride, were significantly reduced. TNP‐coupled macrophages given to animals suppressed both the cell‐mediated and humoral responses, and this might be due to the presence on their surface of TNP‐labeled cytophilic antibody. TNBS administered i.v. binds to circulating proteins and formed blood elements. Thus the split unresponsiveness affecting either humoral or cell‐mediated compartments after the injection of TNP‐MGG or of haptenated cells respectively, is presumably due to dissecting events which in vivo after the injection of TNBS, occur simultaneously. These results may be interpreted to indicate that split unresponsive states to TNP determinants are mediated by two independent mechanisms which require different tolerogen presentations to be triggered.
Human Ia‐like DRw lymphocyte antigens stimulating activity in primary mixed lymphocyte reaction
Authors: Fradelizi D. , Nunez‐Roldan A. , Sasportes Marilyne
Published: February 2007

The intenstiy of the primary mixed lymphocyte reaction (MLR) seems to be influenced by at least two distinct determinants of the HLA‐D region: the HLA‐Dw‐stimulating products and the human Ia‐like B lymphocyte DR (D‐related) antigens. In three families, the primary MLR is significantly higher in case of HLA haploidentity, when stimulating and responding cells differ with regard to both Dw and DRw determinants, than when only Dw products are different. Thus, an additional effect of DR antigens during primary MLR is observed.

The role of DRw antigens in primary MLR and the results obtained by a primed lymphocyte test which can discriminate between Dw3 and DRw3, indicate that DRw and Dw products could be distinct determinants.
Blastogenic factor: its role in the mixed leukocyte culture reaction
Authors: Uotila Marjatta , Rode H. N. , Gordon J.
Published: February 2007

The MLC‐CML reaction depends on cooperation between different subsets of T lymphocytes in which soluble mediators may play a critical role. Evidence is presented that cell‐free supernatants from mixed cultures, containing blastogenic factor (BF) activity can, together with solubilized membrane preparations, induce a primary cell‐mediated lympholysis (CML) reaction of the same order of magnitude as intact allogeneic stimulating cells. Furthermore, BF alone can induce secondary mixed leukocyte culture (MLC) and CML reactions very efficiently. The results described suggest that BF is produced in response to activation by LD determinants, probably by helper T cells, and that the target of BF is the cytotoxic lymphocyte. It would appear that regulation of CML activity may be mediated by BF, and exhaustion of the mediator may be responsible for the decline of cell proliferation and effector function in the MLC reaction.
Regulation of delayed‐type hypersensitivity. II. Specific suppressor factor for delayed‐type hypersensitivit to sheep erythrocytes in mice
Authors: Liew F. Y. , Chan‐Liew W. L.
Published: February 2007

An antigen‐specific suppressor factor for delayed‐type hypersensitivity (DTH) to sheep red blood cells (SRBC) in mice is described. Lymph node cells and spleen cells from mice injected intravenously with 1 × 109 SRBC 4 days previously were incubated in vitro for 48 h in culture medium. Supernatant obtained from the culture inhibited the induction of DTH to SRBC in normal mice. It also suppressed the expression of DTH in presensitized mice. The suppression is specific as the suppressor factor had no effect on the DTH to a noncross‐reacting antigen, chicken red blood cells. Treatment of the spleen cells with anti‐theta serum and complement prevented the production of the suppressor factor, whereas treatment with anti‐Ig serum and complement had no effect. Suppressor factor produced by H‐2k mice suppressed the DTH in H‐2b mice. The factor thus seems to act across the H‐2 barrier. The suppressor factor was not removed by adsorption with goat anti‐mouse immunoglobulin immunoadsorbent, but could be adsorbed by SRBC. It was stable at 56 °C for 1 h, but was partially inactivated by freezing and thawing. The factor has a molecular weight of less than 35 000 daltons.
Grafting of triggering sites onto lymphocytes. Requirement of multivalency in the stimulation of dinitrophenyl‐modified thymocytes by anti‐dinitrophenyl antibody
Authors: Ravid A. , Novogrodsky A. , Wilchek M.
Published: February 2007

N4‐Dinitrophenyl‐L‐2,4‐diaminobutyric acid hydrazide was coupled to aldehyde groups generated by periodate oxidation of sialyl residues on thymocytes. Anti‐2,4‐dinitrophenyl(Dnp)antibody was found to stimulate mature, hydrocortisone‐resistant thymocytes, while it had no mitogenic effect on the immature thymocytes.

In order to study the involvement of different regions of the antibody molecule in the triggering process of stimulation, the mitogenicity of various antibody fragments was also assessed. The divalent F(ab')2 was found to be a superior mitogen compared to the intact antibody when added to Dnp‐conjugated thymocytes. The monovalent Fab' and Fab fragments have no mitogenic activity indicating that cross‐linkage may be a prerequisite for stimulation.
Activation of the alternative complement pathway by human B cell lymphoma lines is associated with Epstein‐Barr virus transformation of the cells
Authors: McConnell I. , Klein G. , Lint T. F. , Lachmann P. J.
Published: February 2007

Activation of the alternative complement pathway by human B cell lymphoma lines is correlated with the presence of Epstein Barr virus (EBV) in the cell genome. EBV‐negative B cell lymphoma lines produce little activation of the alternative pathway as measured either by C3 deposition on the cell surface or C3 conversion and consumption of alternative pathway activity in the supernatant serum. By contrast, EBV‐positive sublines derived by in vitro EBV conversion of EBV‐negative parental lines produce considerable activation of the alternative pathway. This membrane‐associated complement‐activating mechanism reflects an EBV‐induced membrane change in these cells and may provide a mechanism where by EBV‐transformed cells are controlled in vivo.