bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis
Authors: Feingold Nicole , Feingold J. , Mouton Denise , Bouthillier Yolande , Stiffel Claude , Biozzi G.
Published: February 2007

Selective breeding for the character “agglutinin production to heterologous erythrocytes” was performed on random‐bred populations of albino mice. Two types of selection were carried out: Selection I: the first 6 generations were immunized with sheep erythrocytes (SE), then SE and pigeon erythrocytes (PE) were alternated at each generation to avoid the interference of maternal antibody. Selection II: all generations were immunized with SE 60–70 days after weaning in order to eliminate the maternal antibody. Both were selected for the character agglutinin titer 14 days after immunization using an optimal dose of erythrocytes.

Selection I. The mean response to SE of the foundation population was 7.36 ± 1.60. The selection limit was attained between the 15th and the 20th generation. The F20−F30were considered as homozygous for the character investigated. The mean SE agglutinin titers were 9.15 (1/2820) in the high responder line and 2 (1/20) in the low responder line. This corresponds to 140‐fold interline difference in agglutinin titers. SE agglutinins determined in F1 hybrids, F2 hybrids and backcrosses obtained from F23 − F29 demonstrated incomplete dominance of high responsiveness (23–29%).

The inbreeding coefficient produced by close colony breeding was 0.55 in high and 0.71 in low responders at the 20th generation when both lines were homozygous with respect to agglutinin synthesis.

Selection II. The mean response of the foundation population to SE was 7.79 ± 1.56. The selection limit was attained in F14−F17 generations that were considered homozygous for the character investigated. The mean SE agglutinin titer was 9.2 (1/2900) in high responders and 2.8 (1/35) in low responders, which is an 83‐fold interline difference in agglutinin titers. The results of both selections indicate that the character agglutinin synthesis is subject to polygenic regulation. The heritability (h2) of this character was estimated to be between 0.18 and 0.36 (range between the extreme values of Selections I and II).

The attempt to evaluate approximately the number of “loci” is compatible with the hypothesis that a group of about 10 loci regulates the quantitative antibody response. The sources of errors of this evaluation and the significance of the term “loci” are discussed.
Reversible binding of a T cell factor on IgG‐coated Sepharose beads
Authors: Guimezanes A. , Fridman W. H. , Gisler R. H. , Kourilsky F. M.
Published: February 2007

Supernatants of alloantigen‐activated T cells contain a number of factors, including an immunoglobulin‐binding factor (IBF) which inhibits complement‐induced hemolysis of sheep erythrocytes coated with anti‐Forssman IgG anti‐bodies and a factor which suppresses IgM antibody synthesis in vitro. These two factors may be identical, since they are simultaneously retained on Sepharose beads to which IgG has been coupled and can be recovered by elution at pH 2.8. They do not bind to Sepharose beads to which IgM of F(ab′)2 fragment of IgG has been coupled, demonstrating that they have a selective affinity for the Fc region of IgG. In addition, the fixation of IBF on the Fc portion of IgG reversibly inhibits subsequent binding of the first component of complement (C1), thus indicating that IBF does not irreversibly alter the C1 binding site(s) of IgG.
HLA antigens: rabbit antisera reacting with all A series or all B series specificities
Authors: Cresswell P. , Ayres Janet L.
Published: February 2007

Papain‐solubilized HLA antigens giving only two bands of 34 000 mol.wt. and 11 000 mol.wt. by sodium dodecyl sulfate (SDS) gel electrophoresis and isolated from the cultured human lymphoblastoid cell line RPMI 4265, have been used to prepare antisera in rabbits. Antisera were raised against soluble products of the A (or 1st) series of HLA, bearing the determinant HLA‐A2 (A2 substance), or against a mixture of products of the B (or 2nd) series of HLA, bearing the determinants HLA‐B7 and HLA‐B 12 (B7‐12 substances). Rabbit antisera to A2 substance reacted primarily with A2 substance on Ouchterlony analysis, showing an apparent spur of cross‐reactivity with B7‐12 substances. Rabbit antisera to B7‐12 substances reacted primarily with B7‐12 substances, giving a spur of cross‐reactivity with the A2 material. Neither antiserum precipitated β‐2microglobulin. Both types of sera reacted with membrane molecules of 43 000 mol.wt. and 11 000 mol.wt. by immune precipitation and gel electrophoresis in SDS of detergent‐solubilized radiolabeled membranes from cultured cell lines, as predicted for sera directed towards HLA antigens. F(ab′)2 fragments of the antibodies blocked the complement‐mediated cytotoxicity of all HLA alloantisera tested for human peripheral blood lymphocytes. After absorption with B7‐12 substances, F(ab′)2 fragments of antisera to A2 substance only blocked the cytotoxicity of HLA alloantisera to A series specificities. After absorption with A2 substance, F(ab′)2 fragments of rabbit antisera to B7‐12 substances only blocked the cytotoxicity of HLA alloantisera to B series specificities. The results prove the existence of shared antigenic determinants between all members of the same series. These findings support the genetic evidence that A series HLA antigens are allelic products of a single locus, while B series HLA antigens are allelic products of a separate locus, by establishing some invariance of structure, presumably amino acid sequence, between members of the same series. The apparent cross‐reactivity between A2 substance and B7‐12 substances, and the ability of the unabsorbed F(ab′)2, preparations to block the cytotoxicity of all HLA alloantisera, suggests that some determinants are common to both HLA loci. This may be considered to support the hypothesis that the two loci arose by gene duplication.
Structural and immunological similarities between HLA antigens from three loci
Authors: Rask L. , Lindblom J. B. , Peterson P. A.
Published: February 2007

HLA antigens are coded for by three closely linked loci. The gene products of the first and second locus are known to be very similar in overall structure. Antigens coded for by the third locus were examined with regard to their chemical and immunological relationship to the first and second loci gene products. It is demonstrated that the third locus antigens are composed of two types of polypeptide chains, the smaller of which is identical to β2‐microglobulin. The alloantigenic polypeptide chain has an apparent molecular weight of 48 000 when solubilized by detergent treatment and about 35 000 when released from the cell membrane by proteolysis. These data together with size and shape analyses by gel chromatography and sedimentation velocity determinations show that HLA antigens from the three subloci are indistinguishable with the techniques employed. Suggestive evidence was obtained that the third locus antigens are more sensitive to proteolysis than the first and second locus antigens.

The similarity between the three gene products was also evident on cyanogen bromide fragmentation of the polypeptide chains. Furthermore, rabbit antibodies against antigens coded for by the first locus cross‐reacted extensively with antigens from the second and third locus. This study therefore lends strong credence to the view that the three HLA antigen subloci have arisen by gene duplications of a common ancestral gene.
Detection of anti‐idiotype reactive cells in the response to phosphorylcholine
Authors: Cosenza H.
Published: February 2007

Upon immunization with phosphorylcholine (PC), BALB/c mice produce antibodies bearing mainly one idiotype which is identical to that of the TEPC 15 PC‐binding myeloma protein. By coating sheep red cells (SRC) with TEPC 15 it was possible to detect anti‐idiotypic plaques during the course of an immune response to PC. These plaques are detectable only after the anti‐PC response has reached a peak and begun to decline. They are specific, since addition of free TEPC 15 and not MOPC 315 prevented their detection. It is suggested that such anti‐idiotypic reactive cells might regulate the response to PC.
Studies on the lymphocytes of sheep. I. Recirculation of lymphocytes through peripheral lymph nodes and tissues
Authors: Hall J. , Scollay R. , Smith Marilyn
Published: February 2007

Recirculating lymphocytes were collected from the efferent ducts of peripheral somatic nodes and incubated in vitro with 51Cr. After washing, the labeled cells were returned to the sheep by i.v. injection. The partitioning of the labeled cells between blood and efferent (intermediate) lymph, or between efferent and afferent (peripheral) lymph was monitored for the next 24 h by assaying the radioactivity in appropriate samples of cells.

The labeled lymphocytes took several hours to migrate through the nodes so that they equilibrated between blood and lymph in about 10 h. This pattern was not altered grossly during the inductive phase of an immune response.

The small numbers of lymphocytes which migrated through peripheral tissues entered the lymph at least as quickly as those that migrated through lymph nodes.
Correlation of PPD and BCG‐induced leukocyte migration inhibition, delayed cutaneous hypersensitivity, lymphocyte transformation in vitro and humoral antibodies to PPD in man
Authors: Fleer A. , van der Hart Mia , Blok‐Shut B. J. Th. , Schellekens P. Th. A.
Published: February 2007

In a study of healthy human individuals a complete lack of correlation between the results of the agarose leukocyte migration inhibition (LMI) test, using purified protein derivative (of tuberculin) (PPD) and Bacillus Calmette Guérin (BCG) as antigens, and delayed cutaneous hypersensitivity and lymphocyte transformation in vitro to PPD was found. There was a reasonable correlation between PPD‐ and BCG‐induced LMI.

Antibodies to PPD proved to have no influence on PPD‐induced LMI. Purified polymorphonuclear leukocytes, whether derived from donors sensitive to PPD in the agarose LMI test or from nonsensitive donors, did not show migration inhibition to PPD.

It was concluded that polymorphonuclear leukocytes and lymphocytes need to be present simultaneously for migration inhibition of peripheral blood leukocytes by PPD.

Furthermore, because a consistent relation with conventional parameters of cell‐mediated immunity was lacking, it is doubtful whether the agarose LM1 test can be considered as an alternative parameter of this kind of immunity.
B cell tolerance induced by polymeric antigens IV. Antigen‐mediated inhibition of antibody‐forming cells
Authors: Klaus G. G. B.
Published: February 2007

The role of antibody‐forming cell (AFC) blockade in the genesis of hapten‐specific tolerance induced by hapten (2,4‐dinitrophenyl)‐coupled pneumococcal polysaccharide (DNP‐lys‐S3) was investigated. Tolerizing doses of DNP‐lys‐S3 given to mice making antibodies to DNP‐hemocyanin a day before assay markedly reduced numbers of detectable anti‐DNP AFC. Furthermore, anti‐DNP AFC were specifically inhibited by brief in vitro incubation with DNP‐lys‐S3, followed by extensive washing. This inhibition requires multivalent binding of tolerogen to immunoglobulin receptors on AFC, and appears to result from a decrease in the rate of antibody secretion per cell.

A variety of data indicate that IgM AFC are more susceptible to blockade than IgG AFC, and the susceptibility of both cell types decreases with time after immunization. This probably reflects differences in the density and in the rate of loss of surface immunoglobulin receptors on IgM and IgG AFC and their immediate precursors.

However, we conclude that under “conventional” tolerizing conditions, i.e. when tolerogen is given prior to immunogen, DNP‐lys‐S3 suppresses antibody formation primarily by inactivating DNP‐specific precursor cells. AFC blockade is therefore probably only relevant in the suppression of (primary?) IgM responses by large doses of tolerogen. The relative importance of precursor inactivation and AFC blockade in tolerogenesis of IgM responses to T cell‐independent antigens (such as 53) remains to be elucidated.
N‐terminal amino acid sequence of a human delta‐chain myeloma protein
Authors: Milstein Celia P. , Northrop F.
Published: February 2007

The N‐terminal amino acid sequence (26 residues) of a δ‐chain of a human myeloma (Er I) is homologous with the prototype sequence of the human VHIII subgroup. This indicates that the δ‐chain is using for its V region the same pool of V genes as the rest of the immunoglobulin classes. Implications of this finding are discussed.
Enzymatic removal of H‐2 alloantigens from the surface of P815‐(X2) mouse tumor cells
Authors: Thomas K. , Engers H. D. , Cerottini J.‐C. , Brunner K. T.
Published: February 2007

After treatment with papain (6 mg/ml) for 1 h, P815 tumor cells became resistant to complement‐mediated lysis by mouse alloantibodies of different specificities. Immunofluorescence and absorption studies indicated that this resistance was associated with removel of the corresponding antigenic determinants from the cell surface. In contrast, papain‐treated tumor cells were fully susceptible to lysis by rabbit antiserum against P815 cells, indicating a) no alteration of the membrane sensitivity to complement damage, and b) a dissociation between structure and/or localization of allo‐ and xenoantigens.

Papain‐treated cells were also completely resistant to lysis by cytolytic T lymphocytes (CTL) during the first 60 min after completion of the enzyme treatment. Susceptibility to lysis by either CTL or alloantibody and complement reappeared within a few hours after incubation in culture medium and was virtually normal by 6 h. Treatment of P815 cells with trypsin (2 mg/ml) had no effect on either humoral or cellular lytic activities.
Study of A100 allotypic specificity of rabbit immunoglobulins The cross‐reactivity between A100, a1 and a3
Authors: Cazenae P.‐A. , Bréezin Colete
Published: February 2007

Evidence for the genetic determination of A100 allotypic specificity suggests that it is the product of an allele at the a locus. The A100 allotypic specificity was detected in a wild rabbit lacking all the known specificities of the a series. None of the 8 rabbits possessing the A100 allotypic specificity possessed two allotypic specificities of the a series. The concentration of A100+ molecules is larger in the serum of a presumably homozygous rabbit than in that of a presumably heterozygous rabbit. In the sera of heterozygous A100+ rabbits, the A100 allotypic specificity and the known specificity of the a series are carried by different molecules. The determinants responsible for the A100 allotypic specificity are present both on IgG and IgM. They are located on the heavy chain and the Fab fragment of IgG. A family of variants of A100 specificity has been detected and cross‐reactivity between A100, a1 and a3 specificities has been found. This was detected and studied with anti‐a3 antisera. It seems that A100 allotypic specificity is closer to a3 specificity than a1 is to a3 specificity.
Suppressor cell induction in vitro. II. Cellular requirements of suppressor cell induction
Authors: Feldmann Marc , Kontiainen S.
Published: February 2007

The cellular requirements for the induction of antigen‐specific suppressor cells (SC) in vitro were studied. Macrophage depletion, by either nylon wool or polystyrene columns or iron (and magnet) treatment or a combination of methods, did not diminish SC induction, in contrast to its effect on helper cell induction. The requirement for T‐T interaction in SC induction using splenic T cells was studied by the use of adult thymectomy and antilymphocyte serum, which selectively deplete short‐lived and recirculating T cells respectively. Since suppressor cell induction was markedly diminished, or abolished by either procedure, but reconstituted by mixing these 2 populations, it was concluded that there was T‐T interaction in the development of SC, just as there is in the induction of other T cell reactions, such as the graft‐versus‐host response, the T killer cell response, the helper cell response and, tentatively, delayed hypersensitivity. By the use of double‐chamber tissue culture flasks, with the 2 cell populations separated by a cell impermeable membrane, it was found that T‐T interaction does not require cell contact and is thus mediated by factor(s). The direct precursor of antigen‐specific suppressor cells is resistant to adult thymectomy but sensitive to anti‐lymphocyte serum.
Lymphocyte‐mediated cytotoxicity against tumor cells. II. Characteristics and tissue distribution of concanavalin A‐ activated cytotoxic effector cells
Authors: Waterfield J. D. , Waterfield Elizabeth M.
Published: February 2007

In vivo or in vitro activation of cytotoxic effector lymphocytes by concanavalin A (Con A) has been shown to result in a population of effector cells exhibiting a degree of immunological specificity when Con A was present during the cytotoxic assay (Waterfield, J.D. et al., Cell. Immunol. 1975. 17: 392). In this communication we have characterized the Con A‐activated effector cell by physical criteria and tried to assign it to a given subpopulation of thymus‐derived lymphocytes. It was shown that macrophages played no role in target cell lysis in this system, nor was their presence required for Con A activation of the effector cell. The effector cell proved insensitive to anti‐Θ serum, but was classified as a T cell by the enrichment of cytotoxicity when a purified population of T cells was activated by Con A in vitro and by the failure to activate the effector cell in nude mice. Precursors of the effector cell were shown to reside primarily in the spleen, to be radioresistant up to 400 R, and to be short‐lived after adult thymectomy. Thus, the effector cell can be classified with the TI population of T cells and has similar characteristics as a cytolytically active cell described by Stobo et al. (J. Immunol. 1973. 110: 362, 652).
Lymphocyte‐mediated cytotoxicity against tumor cells. III. Differentiation of concanavalin A‐activated cytotoxic effector cells
Authors: Waterfield J. D. , Waterfield Elizabeth M.
Published: February 2007

The maturation of selected T cell responses in the lymphoid organs of irradiated CBA mice was followed after adoptive transfer of syngeneic fetal liver cells. Mitogenic responsiveness to phytohemagglutinin (PHA) and concanavalin A (Con A) was found to reach control values 3 weeks after reconstitution in the thymus, spleen, and lymph node, of fetal liver repopulated animals. Spleen and lymph node cell reactivity in mixed lymphocyte culture reactions required 6 weeks to reach significant values. However, the ability of spleen cell suspensions to be activated by Con A into cytotoxic effector lymphocytes appeared after only 2 to 3 weeks. It is concluded that two functionally distinct T cell subpopulations exist in the spleen, one which can be activated into cytotoxic effector lymphocytes by Con A, and one which responds to alloantigens by DNA synthesis.
An ultrastructural study of two different responses of mouse mast cells to transplantation antibodies directed against the same transplantation antigens
Authors: Le Bouteiller Ph. , Daëron M. , Duc H. T. , Righemi S. , Voisin G. A.
Published: February 2007

The present paper describes an ultrastructural study of two different kinds of behavior of mouse mast cells during two immunological reactions induced by transplantation antibodies: the direct allogeneic anaphylactic degranulation and the serocytotoxicity. In both situations, the same alloantigens, born by the mast cells themselves, are the targets of the reaction, but the first one is mediated by anaphylactic alloantibodies whereas the second one is mediated by cytotoxic alloantibodies in the presence of complement. The comparison of the ultrastructural aspects of the cells in these two systems demonstrated that mast cells can behave in two different ways depending on the nature of the immunological agents utilized. First, a physiological degranulation process with active granule expulsion was observed. This process was shown to be identical to the one induced in classical in vitro anaphylaxis or by histamine releasers such as compound 48/80. A second type of behavior was a lethal, complement‐ dependent, cell lysis without active granule expulsion.
Role of macrophages in the generation of T helper cells. IV. Nature of genetically related factor derived from macrophages incubated with soluble antigens
Authors: Erb P. , Feldmann Marc , Hogg Nancy
Published: February 2007

Macrophages incubated with soluble antigens for 1–4 days release factors capable of inducing T helper cells. The nature and some of the properties of this genetically related macrophage factor (GRF) were investigated. By use of immunoadsorbents, GRF was shown to contain I region‐coded products (Ia antigens) linked to a small antigenic fragment. The genes coding for the Ia antigens detectable in GRF lie in the I region of the H‐2 complex.

GRF does not react with anti‐immunoglobulin, anti‐C3 or anti‐human β2‐ microglobulin antisera, and its activity cannot be removed by antigen immunoadsorbents. GRF is heatlabile, sensitive to proteolytic enzymes and has a molecular weight of about 55 000 Daltons. The relationship of GRF to other factors known to contain I region‐coded products and reported to be effective in cell cooperation is discussed.
In vitro synthesis of factor B of the alternative pathway of complement activation by mouse peritoneal macrophages
Authors: Bentley Carolyn , Bitter‐Suermann D. , Hadding U. , Brade V.
Published: February 2007

Factor B of the alternative pathway of complement activation was shown to be synthesized and secreted by unstimulated mouse peritoneal macrophages. The activity of B in the culture supernatants from macrophage monolayers was detected by consumption of C3 in reaction mixtures containing supernatant and guinea pig factors C3, D and insoluble C3b. Using a monospecific antiserum, factor B in concentrated culture supernatants was shown by immunodiffusion and immunoelectrophoresis to be identical to factor B in mouse plasma and to form a characteristic complex with cobra venom factor in the presence of D. A steady rate of factor B secretion was observed for 4 days providing the medium was changed every 24 h. Cycloheximide (0.5 μg/ml), an inhibitor of protein synthesis, caused inhibition (90%) of factor B production. Incubation of culture medium containing 14C‐labeled amino acids with the macrophage monolayer resulted in incorporation of radioactivity into factor B as detected by autoradiography of precipitation lines formed with anti‐B antiserum. This indicated that synthesis of factor B had occurred. In the same culture supernatants the presence of newly synthesized C3 was also demonstrated.
Antibody response to phosphorylcholine in vitro. II. Analysis of T‐dependent and T‐independent responses
Authors: Quintáns J. , Cosenza H.
Published: February 2007

Spleen cells, from BALB/c mice primed with keyhole limpet hemocyanin (KLH), were stimulated with heat‐killed vaccine of rough Pneumococcus pneumoniae R36A (Pn) and/or phosphorylcholine (PC)‐coupled KLH to induce an anti‐PC response in vitro. The response to PC‐KLH was found to be T‐dependent while it is T‐independent to Pn. The antibodies induced with either antigen had similar avidity and expressed the TEPC 15 idiotype exclusively; thus T cell involvement in the response to PC‐KLH failed to alter these parameters of the anti‐PC response.

At the precursor cell level, Pn induced small clones with an average size of 10 plaque‐forming cells (PFC), whereas PC‐KLH gave rise to larger clones of 40–50 PFC. This difference in the proliferative potential of PC precursor B cells hinted at the possibility that Pn and PC‐KLH were stimulating different precursors. This was corroborated by the observation that a) when Pn and PC‐KLH were added to the same cultures a synergistic effect was seen, i.e. the number of plaques was greater than the sum of the responses induced by each antigen, and b) in microcultures, under conditions limiting B cells only, Pn plus PC‐KLH induced a higher fraction of responding wells than either antigen on its own. We postulate that Pn and PC‐KLH stimulate subpopulations of PC precursor cells which are T‐independent and T‐dependent, respectively.
Cellular reaction induced by “nonantigenic” substances
Authors: Sabolović D. , Oth D. , Bujadoux Madeleine
Published: February 2007

A previously designed isotopic in vivo method for measuring delayed hypersensitivity was used with nonantigenic (or weakly antigenic) phlogogenic substances. A strong reaction was observed in some circumstances, witnessing the fact that the method has a specific and a nonspecific component. The reaction is drastically augmented by a mild whole‐body irradiation of the reacting animals. In the case of the studied substances (carbon, oil and bentonite) the reaction is bound by polymorphonuclear neutrophils (PMN), but it was found to be independent of the number of circulating PMN in the blood.
Efferent enhancement of a methylcholanthrene‐induced Sarcoma transplantable in strain 13 guinea pigs
Authors: Berczi I. , Tsay H.‐M. , Sehon A. H.
Published: February 2007

The immunobiology of an antigenic methylcholanthrene‐induced sarcoma (MC‐D) of inbred strain 13 guinea pigs has been investigated. The induction of concomitant immunity by growing MC‐D tumors was indicated by the suppression of small tumor inocula in the presence of a large tumor cell dose and by the regression of intradermal tumor nodules. Furthermore, it was demonstrated that this tumor was coated with antibody in vivo. Previous studies showed that MC‐D tumors were infiltrated with killer T cells which were capable of complete tumor destruction in vitro, but could never induce spontaneous regression in vivo. On the basis of all these facts, antibody‐mediated efferent enhancement is proposed to be the major escape mechanism of this tumor.
Expression of new idiotypes following neonatal idiotypic suppression of a dominant clone
Authors: Augustin A. , Cosenza H.
Published: February 2007

The anti‐PC antibodies of BALB/c origin bear predominantly the idiotype characteristic of the phosphorylcholine (PC)‐binding T15 myeloma protein. Sera from one‐day‐old BALB/c mice contain lower amounts of T15 idiotype than sera from adult mice, and, unlike the latter, they also contain detectable amounts of anti‐T15 antibodies. By 2 weeks of age the anti‐T15 antibodies are no longer detectable while the T15 idiotype has reached adult levels. Injection of neonatal mice with anti‐idiotypic antibodies renders them unresponsive to PC until the 15th week of life. Furthermore, this treatment induces a chronic suppression of the T15 idiotype, since on recovery from unresponsiveness, the neonatally suppressed mice produce anti‐PC antibodies which are predominantly T15‐negative. In contrast, treatment of adult mice with anti‐idiotypic antibodies induces only a transient state of unresponsiveness to PC, and the antibodies produced upon recovery bear the T15 idiotype. These findings are discussed in the context of idiotype anti‐idiotype interactions and their possible role in immunoregulation.
Derivation of specific antibody‐producing tissue culture and tumor lines by cell fusion
Authors: Köhler G. , Milstein C.
Published: February 2007

Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody‐producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody‐producing tumors in mice.

Spleens from mice immunized against sheep red blood cells (SRBC) were fused to an 8‐azaguanine‐resistant clone (X63‐Ag8) of MOPC 21 myeloma. Over 50 % of the derived hybrid lines produce and secrete immunoglobulins different from the MOPC 21 myeloma. About 10 % of the hybrid lines exhibit anti‐SRBC activity. The high proportion of antibody‐producing hybrids suggests that the fusion involves a restricted fraction of the spleen cell population, probably cells committed to antibody production.

In order to avoid the presence of the MOPC 21 heavy chain in the specific hybrids, another myeloma cell line (NSI/1‐Ag4–1) has been used. This is a nonsecreting variant of the MOPC 21 myeloma which does not express heavy chains.

Three anti‐SRBC (probably of the μ, γ2b and γ1 classes, respectively) and two anti‐2,4,6‐trinitrophenyl (of the μ class) antibody‐producing hybrids have been repeatedly cloned. By random selection and by selection of specific clones according to their lytic activity (clone plaque selection), a number of different lines have been constructed. Such lines express different combinations of the four possible chains of each hybrid line: the myeloma γ and k chains and the specific antibody heavy and light chains. In three cases (Sp1, Sp2 and Sp7) it is shown that only the specific H and L combination has activity and that the myeloma chains are unable to substitute for them. In most cases lines have been derived which no longer express the MOPC 21 chains but only the specific antibody chains.
Reconstitution of genetically regulated responses against random and ordered synthetic polypeptides by methylated bovine serum albumin as analyzed by isoelectric focusing
Authors: Cramer M. , Schwartz Michal , Mazes Edna , Sela M.
Published: February 2007

In previous publications it was shown by avidity measurements, cross‐reactivity patterns and genetic analyses, that the tetrapeptide T‐T‐G‐G is the immunodominant epitope of the synthetic polypeptide (T, G)‐A–L. In the present study this close immunological relationship between the random multichain copolymer (T, G)‐A–L and the ordered analogue (T‐T‐G‐G)‐A–L is extended by two additional criteria. First, the immune response against (T‐T‐G‐G)‐A–L in H‐2k nonresponder mouse strains can be reconstituted to high antibody levels by complexing this antigen to methylated bovine serum albumin, as was tested earlier for (T, G)‐A–L. The antibodies elicited upon reconstitution in both antigenic systems are directed mainly against the same determinant, T‐T‐G‐G. Second, isoelectric focusing analysis of specific antisera developed with radiolabeled antigen revealed restricted 7 S IgG antibody populations in high responder and reconstituted high and low responder mice. The spectra were found to be of similar complexity in the (T, G)‐A–L and in the (T‐T‐G‐G)‐A–L system. From these data it was concluded that the repertoires of specific B cells to T‐T‐G‐G are very similar in high and low responder strains, and the defect in the H‐2k low responder systems should be located at the level of T‐B cell cooperation.
Functional half‐life of virgin and primed B lymphocytes
Authors: Elson C. J. , Jablonska K. F. , Taylor R. B.
Published: February 2007

The functional half‐life, a measure of the persistence of lymphocytes in an antigen‐free environment, has been estimated and found to be about 7 days for virgin 2,4,6‐trinitrophenyl (TNP)‐reactive mouse B cells, and 2–3 times longer for TNP‐primed B cells. Using allotype‐congenic mice, lymph node cells were transferred from virgin or primed CBA/Igb donors to normal CBA/Iga recipients, and the proportion of donor B cells estimated at intervals. This was done by making a further transfer to irradiated recipients and challenging with a TNP conjugate. The donor contribution declined with time in approximately exponential fashion to give the functional half‐life. The experiment with primed cells necessitated mixing them with virgin cells, and thus allowed the possibility of interactions. However, control experiments showed that, at least in the final transfer, the primed cell response was not decreased by the presence of excess virgin cells ‐ although primed cells suppressed virgin cells. In other experiments where the intermediate hosts were treated with vinblastine, it was shown that primed B cells have a slower turnover rate than virgin B cells. The relevance of these results to the problem of B cell tolerance is discussed.
T cell requirements for the expression of the lipopolysaccharide adjuvant effect in vivo: evidence for a T cell‐dependent and a T cell‐independent mode of action
Authors: Ness Dolly B. , Smith S. , Talcott J. A. , Grumet F. C.
Published: February 2007

The in vivo adjuvant effect of lipopolysaccharide (LPS) in mice was investigated with the soluble synthetic polypeptide antigen (T, G)‐A–L, the antibody response to which is determined by the Ir‐1A gene. With this specific antigen it can be demonstrated that the LPS adjuvant effect has the following modes of action: a) a T cell‐independent enhancement of primary and secondary IgM antibody response; b) a T cell‐dependent enhancement of IgG secondary antibody response; and c) a T cell‐dependent induction of switchover from IgM to IgG antibody in some strains of Ir‐1A low responders. Although T cells are necessary for some aspects of the adjuvant effect, these data do not distinguish between a mechanism involving a direct interaction between LPS and T cells or a direct interaction of LPS and B cells with a general requirement for T cells for expression of IgG antibody.
T lineage lymphocytes in nude mice born from homozygous nu/nu parents
Authors: Loor F. , Amstutz Heidi , Hägg Lena‐Britt , Mayor Kathleen S. , Roelants G. E.
Published: February 2007

T lineage cells are found in the spleen of neonatal nu/nu mice born from nu/nu x nu/nu matings, and also in old, healthy nude mice obtained from the usual nu/+ x nu/nu matings. Their presence in neonatal nude mice which were never in contact with mother or normal littermate thymus products shows that commitment of stem cells towards the T lineage does not require the influence of the thymus.
The xenogeneic effect – Evidence for coparticipation of human monocytes and T lymphocytes in the restoration of nude mouse in vitro response to sheep red blood cells
Authors: Estroff T. , Galanaud P. , Dormont J. , Wallon Christine , Tchernia G.
Published: February 2007

The restorative ability of human peripheral blood lymphocyte fractions on nude mouse spleen cell in vitro antibody response to SRBC was studied. Strongly adherent cells (monocytes) enhanced nude cell response, but not to the same extent as the optimal number (106) of unfractionated human peripheral blood lymphocytes. T‐depleted cells lost their ability to optimally restore the response, while T‐enriched cells showed a definite restorative ability. The recombination of adherent cells with T‐enriched cells produced an effect comparable to that of unfractionated cells, both in terms of magnitude and dose‐response curve. These data suggest that both monocytes and T cells are necessary for an optimal xenogeneic effect in Mishell‐Dutton cultures.
Adult thymectomy prevention of the appearance of suppressor T cells which depress contact sensitivity to picryl chloride and reversal of adult thymectomy effect by thymus extract
Authors: Asherson G. L. , Mayhew Barbara , Zembala M. , Goldstein A.
Published: February 2007

Suppressor cells, which depress the passive transfer of contact sensitivity appear in the lymph nodes and spleen of mice injected with picryl sulfonic acid (PSA). These cells produce a soluble suppressor T cell product (s‐TCP), and immune lymph node cells incubated in s‐TCP fail to transfer contact sensitivity. This paper shows that the appearance of suppressor T cells following the injection of PSA was prevented by adult thymectomy (ATx).

ATx also limited the production of s‐TCP. However, ATx had no effect on the DNA synthesis which occurs in the lymph nodes of mice injected with PSA.

The adverse effect of ATx on suppressor cells was completely reversed by a neonatal thymus graft placed under the renal capsule and partially reversed by grafts given 600 r in vitro and to a limited extent by grafts given 1000 r. The injection of thymus extract also reversed the effect of ATx‐whereas splenic extract was inactive. It is suggested that the suppressor T cell which depresses contact sensitivity is dependent on the presence of the thymus because it requires a thymus hormone, and not primarily because it belongs to a short‐lived population which is rapidly renewed by cells coming from the thymus.
Structural and serological relationships among different antibodies from the same rabbit antiserum. II. The idiotypes of ten antibody components from an anti‐streptococcal serum
Authors: Aasted B. , Kindt T. J.
Published: February 2007

In studies aimed at elucidation of the idiotypic relationships among antibodies produced by a single rabbit, ten antibodies were isolated from the serum of a rabbit immunized with streptococcal Group C vaccine. Four of these antibodies were obtained in amounts sufficient to prepare homologous (rabbit) anti‐idiotype antisera. The antisera were used to test for cross‐reactivities among all ten antibodies by binding and inhibition of binding assays. Idiotypic cross‐reactions among the antibodies were detected by three of the four antisera, while the fourth antiserum reacted only with the antibody that was used as the immunogen for its preparation. Two antibodies demonstrating the highest degree of cross‐reactivity had readily distinguishable VH allotypic (a 1) subspecificities. The idiotypic reactions and cross‐reactions could be inhibited by haptens prepared from the Group C carbohydrate. Bleedings taken from the three immunization periods of this rabbit indicated that the four idiotypes were expressed in approximately equal amounts in each immunization period and that all idiotypes dropped to undetectable levels between immunization periods.
Blockade of specific antibody‐forming cells in vivo by dextrans and levans
Authors: Moreno C. , Hale Christine
Published: February 2007

Fractions of dextran (DE) B512, DE B1355 and levan (LE) have been shown to induce a specific blockade of antibody‐forming cells (AFC) when injected into previously immunized mice. Whereas specific blockade with DE B512 (450 000 daltons) was easily induced by as little as 10 μg, blockade to LE and DE B1355 was more resistant and required 1 and 10 mg, respectively.

AFC blockade and tolerance are dissociable phenomena, as the former effect could be achieved with nontolerogenic low mol. wt. DE B512 (10 000 daltons). Conversely, perennial rye grass fructosan (7600 daltons), which is tolerogenic for LE, did not induce blockade. Furthermore, blockade of anti‐DE response specific for α(1→3)‐linked glucosyl determinants was achieved in BALB/c mice, whereas attempts to induce stable tolerance have been unsuccessful.
β2‐Microglobulin distribution in human normal tissues
Authors: Governa M. , Biguzzi S.
Published: February 2007

The distribution of β2‐microglobulin in human normal tissues was investigated by the indirect immunofluorescent antibody method. Lymphoid, macrophage and endothelial cells were consistently positive in every organ studied. In addition, only the stratum germinativum of the epidermis, some tracts of the columnar epithelium of the digestive system and some endometrial tubular glands showed a specific fluorescence.
Relationship between 4a and 4b H LA‐determined specificities and C3 receptors of leukocyte membrane
Authors: Ferreira A. , Nussenzweig V. , Fotino Marilena
Published: February 2007

Contrary to previous reports, we do not find that antibodies to 4a and 4b human histocompatibility antigens inhibit the binding of erythrocytes coated with C3 to the C3 receptor of human monocytes or B lymphocytes.
The “natural killer” cell in the mouse does not require H‐2 homology and is not directed against type or group‐specific antigens of murine c viral proteins
Authors: Becker Susanne , Fenyö Eva Maria , Klein Eva
Published: February 2007

A number of lymphoma lines were characterized for sensitivity to natural killer (NK) cells present in the spleen in young CBA mice and reactivity with antisera directed against certain C‐type virus‐determined proteins expressed on the cell surface. Since no correlation was found, it is likely that the target of the NK cell is neither the antigen(s) recognized serologically by mice nor the group‐specific antigenic determinants of the viral proteins. Various target and effector cell combinations with regard to H‐2 composition did not indicate that H‐2 homology is necessary for the NK effect.
Anomalous reactivity of anti‐T cell sera on spleen cells from T‐cell‐deprived mice and on mitogen‐stimulated nude mice spleen cells
Authors: Twiddy R. R. , Man M. S. , Kerbel R. S.
Published: February 2007

Recent results have shown that various alloantisera which react in the expected fashion on lymphocyte populations can react anomalously against cultured tumor cell populations because of the presence of contaminating antibodies against murine leukemia virus (MLV) antigens. Since it is now known that activation of MLV can occur in certain types of dividing lymphocyte populations, anti‐T cell sera were tested on lymphoid cell populations in which T cells were absent or greatly reduced in numbers, but where activation of MLV in the B cell population would be expected. Whereas normal, freshly harvested, nude mice spleen cells were unreactive, in vitro:stimulation of these cells with the B cell mitogen, lipopolysaccharide, led to a high degree of sensitivity to the cytotoxic effects of anti‐T alloantisera or heteroantisera. Spleen cells from adult thymectomized, lethally‐irradiated, bone marrow‐reconstituted mice also showed unexpected reactivity with the anti‐T cell sera. In both cases, reactivity was noted only if absorbed rabbit serum was used as a complement source in the cytotoxic assays. The anomalous anti‐B cell activity of the anti‐T cell sera could be removed by absorption with relatively small numbers of cells from Thy‐negative cultured tumor cell lines, including fibrosarcomas, but not by absorption with thymocytes.

Hence, activated or stimulated B cells may react strongly with allo‐or hetero‐ anti‐T cell sera under certain conditions, and this anomalous reactivity appears unrelated to the presence of the anti‐T cell antibodies in the sera.
Diseases caused by reactions of T lymphocytes to in compatible structures of the major histocompatibility complex. I. Autoimmune hemolytic anemia
Authors: Gleichmann E. , Gleichmann Helga
Published: February 2007

The capacities of various lymphoid cells from C57BL/10 donors to induce antibodies against red blood cells (RBC) in (C57BL/10 × DBA/2)F1 recipients were compared: cortisone‐resistant thymocytes were more potent inducers than spleen cells, and bone marrow cells were ineffective. This established a need for parental T lymphocytes in the induction of Coombs‐positive hemolytic anemia by the graft‐versus‐host reaction (GVHR). Since some of the anti‐RBC antibodies carried the Igc allotype specific for the F1 host, they were autoantibodies.

When antibodies were eluted from the erythrocytes of F1 mice undergoing the GVHR (GVH F1 mice) and subsequently tested against normal RBC in the indirect Coombs' test, the Igc allotype was demonstrable even on those antibodies found to react with RBC of the donor strain (C57BL/10). In addition, reactions with normal intact RBC of other strains and species were noted. Anti‐RBC antibodies belonged to all Ig classes and subclasses that were tested (IgG1, IgG2a, IgG2b, IgA, and IgM).

By means of histocompatibility typing it was shown that the overwhelming majority of lymphoid cells from GVH animals were host cells; most of these host cells were Thy‐1.2‐negative. In several GVH F1 mice Coombs‐positive erythrocytes were demonstrated for periods of more than 5 months; Igc‐positive anti‐RBC antibodies were detected for periods up to 3 months. When an additional injection of parental T cells was administered to GVH F1 mice, which had become Coombs‐negative in the course of the GVHR, new anti‐RBC antibodies appeared. In contrast to F1 B cells, T cells of the F1 host were not needed for autoimmunization as shown by the induction of anti‐RBC auto‐antibodies in F1 recipients that were depleted of autologous T cells prior to the administration of parental T cells.

When (C57BL/10 × DBA/2)F1 mice were back‐crossed into strain C57BL/10 and the offsprings injected with C57BL/10 (H‐2bb) lymphoid cells, most of the H‐2 heterozygous (H‐2bd) back‐crosses developed Coombs'‐positive hemolytic anemia, whereas none of the H‐2 homozygous (H‐2bb) ones did.

The most likely explanation of these results is that anti‐RBC autoantibodies were induced by a persistent reaction of parental T helper cells to incompatible H‐2 structures on normally present autoreactive F1 B cells. The hypothesis is proposed that reactions of T lymphocytes against virally or chemically altered structures of the major histocompatibility complex may lead to autoimmunization also in nonchimeric individuals.
Mapping of the HLA locus controlling C2 structural variants and linkage disequilibrium between alleles C22 and Bw15
Authors: Meo T. , Bernoc Marietta , Bernoco D. , Ceppellini R. , Atkinson J.
Published: February 2007

The newly discovered polymorphism of human C2 protein analyzed by isoelectric focusing is controlled by a locus closely linked to HLA. An informative cross‐over family (HLA: A×C) indicates that this locus maps on the C side of the region. Population and family studies have shown that the C22 variant is significantly associated on the haplotype with alleles Bw15 and Cw3. The fact that the “deficient” C2 mutant is in linkage disequilibrium with other HLA antigens, suggests that C22 and C20, here tentatively considered alleles of the same locus, are not directly related by descent.
Selective activation of human suppressor cells by a nonproliferative stimulus
Authors: Sondel P. M. , Jacobson M. W. , Bach F. H.
Published: February 2007

The eliciting of suppressor cell activity by heat‐treated stimulating cells demonstrates that suppression can be induced by an antigenic but non‐effective mixed lymphocyte culture (MLC) stimulus in vitro. Simultaneous or prior MLC or cytotoxic T lymphocyte activity is not required for alloantigen‐induced suppressor cell activation.
The role of leukocyte subpopulations in the indirect leukocyte adherence inhibition assay in the mammary tumor virus system
Authors: Creemers Paula
Published: February 2007

A modification of the leukocyte adherence inhibition test for the detection of cellular immunologic reactivity of mice to the mammary tumor virus (MTV) has been described. It involves the transfer of the leukocyte adherence inhibition factor (LAIF) produced by spleen cells from immunized animals when cultured with antigen to indicator cells, for which peritoneal exudate cells from normal mice are used. The method proves to be sensitive and highly reproducible. By crude separation of leukocyte subpopulations it became established that for the production of LAIF the following sequence is needed: 1. incubation of adherent cells with MTV; 2. transfer of a soluble factor SF1 produced by the adherent cells to T cells; 3. transfer of another soluble factor SF2 released by T cells to the adherent cells.