bluuebunny/crossref_metadata_2025 huggingface dataset:
Specific control of responsiveness by two complementing Ir loci in the H‐2 complex
Authors: Melchers Inga , Rajewsky K.
Published: February 2007

H‐2‐linked immune response (Ir) genes specifically and distinctly control immunological responsiveness of mice to the non‐cross‐reacting enzyme antigens LDHA and LDHB. In a previous study (Melchers, I., Rajewsky, K. and Shreffler, D. C., Eur. J. Immunol. 1973. 3: 754) two levels of responsiveness to LDHB were found and mice could be classified into high and low responders (HR or LR). We now detect a third, intermediate level of responsiveness. In addition, in certain crosses, “superhigh” responses as well as responses in between the low and intermediate level are found. An apparently highly polymorphic system of Ir genes thus determines the level of responsiveness in a surprisingly discrete and precise way.

In general, high or intermediate responsiveness was dominant over low responsiveness in F1 animals. In one out of four cases the cross between an intermediate responder (IMR) and a LR, which were congenic for H‐2, resulted in a level of responsiveness in between that of the two parental strains.

In crosses between IMR strains, the F1 animals were either again IMR or showed functional complementation to high responsiveness in two out of four combinations. The results can be explained in terms of two polymorphic loci which interact in the control of responsiveness to LDHB.

Surprisingly, the B10.HTT strain, which carries the recombinant H‐2t3 chromosome, is an IMR, although the H‐2t3 chromosome carries the HR H‐2s allele in the Ir‐1B region, to which Ir‐LDHB has been previously mapped. Complementation to high responsiveness is achieved when the H‐2t3 chromosome is combined in an F1 cross with the H‐2 chromosome from LR strains carrying “silent” HR alleles in the I‐C and/or S regions (H‐2a and H‐2h2).

This demonstrates that the response to LDHB is controlled by at least two separate, interacting loci within the H‐2 complex. One of these loci maps, at least in the case of H‐2s and H‐2d, to the left of the I‐C region, whereas the other is located in I‐C or S, as again shown for the H‐2d and H‐2s haplotypes. One may speculate that these loci also mediate complementation between our IMR strains (see above) and exert distinct functions in the Ir gene control of the immune response.
The role of macrophages in the generation of T helper cells. III. Influence of macrophage‐derived factors in helper cell induction
Authors: Erb P. , Feldmann Marc
Published: February 2007

Helper cell induction to soluble or particulate antigens in vitro requires the cooperation of T cells and macrophages. A direct contact between macrophages and T cells is not obligatory for this cooperation and factors released from macrophages are as effective in activating T cells as the cells themselves. Two different types of macrophage‐derived factors where found. The supernatant obtained from purified macrophages incubated with antigen for several days generates helper cells in absence of macrophages or additional antigen, but only if obtained from macrophages which were identical at the I‐A subregion of the H‐2 complex as the T cells. This factor was called genetically related macrophage factor (GRF). The other factor(s), which is present in the supernatant obtained from macrophages incubated for several days without antigen, replaces macrophages only if the antigen is particulate. This factor(s), called nonspecific macrophage factor (NMF) is not restricted genetically and is also obtained from allogeneic macrophages. The importance of both these factors in helper cell induction is discussed.
Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: conjugation, killing and recycling at the single cell level
Authors: Zagury D. , Bernard Jacky , Thierness Noelle , Feldman M. , Berke G.
Published: February 2007

Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes have been achieved. Peritoneal exudate cytotoxic lymphocytes were obtained from BALB/c mice injected with EL4 tumor cells. Lymphocyte tumor cell conjugation was promoted by centrifugation. Individual conjugates comprised of one lymphocyte bound to one tumor cell were isolated with a micropipette. The ultrastructure of isolated killer lymphocytes and the lysis of conjugated target cells were analyzed. The cytotoxic lymphocytes are small cells with an indented nucleus which is poor in peripheral chromatin and rich in rough nuclear sap. The cytoplasm contains one‐membrane‐bound lysosome‐like granules and clusters of ribosomes, but no rough endoplasmatic reticulum. The Golgi apparatus is well developed. Direct evidence obtained at the single cell level shows that a single effector lymphocyte is required and sufficient for the destruction of a single target cell and that killer cells which have been responsible for the lysis of a given target cell can lyse a second and even a third time.
Genetics of restricted antibodies to streptococcal group polysaccharides in mice II. The Ir‐A‐CHO gene determines antibody levels, and regulatory genes influence the restriction of the response
Authors: Cramer M. , Braun D. G.
Published: February 2007

The immune response of mice to the cell wall polysaccharide of group A streptococci is controlled by a single, autosomal gene, the Ir‐A‐CHO. Ir‐A‐CHO appears to occur in the form of three alleles: allele a determines high responsiveness; it is dominant over allele b, which confers low responsiveness. The combination of allele a with a proposed second low responder allele c leads to intermediate immune responses. Ir‐A‐CHO is not linked to the locus that controls hair color, the agouti‐locus, nor is it linked to the CH allotype or the H‐2 complex.

In addition to Ir‐A‐CHO the immune response to the streptococcal group A polysaccharide is controled by genes which determine the heterogeneity of the response. This complex but nevertheless limited set of genes is autosomal, codominant and generally has no specificity with respect to the expression of a certain set of variable region genes of antibodies. These traits must be regarded as regulatory genes whose control is independent of the CH allotype.
Specificity of Fc receptors of activated T cells. Relation with released immunoglobulin‐binding factor
Authors: Neauport‐Sautes Catherine , Dupuis Dominique , Fridman W. H.
Published: February 2007

This paper deals with the specificity of the receptor for immunoglobulins expressed on activated T cells (ATC) and its relation to immunoglobulin‐binding factor (IBF) produced in vitro by ATC.

By indirect immunofluorescence and rosette techniques, it is shown that Fc receptors are expressed on a subpopulation of cells and are not species specific. Using inhibition techniques, we show (a) that rabbit or human IgG compete with mouse IgG for the fixation on the Fc receptor of mouse ATC, and (b) that the receptor is specific for the C‐terminal portion of the Fc fragment. These properties are shared by IBF. Moreover, incubation of ATC at 37°C provokes a decrease in Fc receptor positive cells and an increase in production of IBF into the supernatant. Both events are blocked by inhibitors of protein synthesis. In addition, degalan beads coated with IgG‐anti‐IgG complexes retain both IBF‐producing cells and Fc receptor‐bearing cells.

These data suggest a relationship between the expression of Fc receptors at the surface of ATC and the release of IBF.
Genetically controlled immune responses of inbred mouse strains to conjugates of the ordered peptides (Tyr‐Tyr‐Glu‐Glu) and (Tyr‐Glu‐Tyr‐Glu) with multichain poly‐DL‐alanine as compared with the response to the random (T, G)‐A‐‐L
Authors: Schwartz Michal , Mozes Edna , Sela M.
Published: February 2007

In previous studies we have shown that the immune response of different inbred mouse strains to the ordered synthetic antigen (Tyr‐Tyr‐Glu‐Glu)‐A‐‐L is similar to that observed with the random polypetide (T, G)‐A‐‐L in the pattern of response and in the cross‐reactivity of specific antibodies with it. By inhibition studies of the hemolytic plaque‐forming cell (PFC) assay we have now further confirmed that T‐T‐G‐G is the major determinant in the random (T, G)‐A‐‐L.

C3H/HeJ mice were found to be nonresponders to (T‐T‐G‐G)‐A‐‐L, whereas using the same techniques these mice produced low titers of antibodies to the random (T, G)‐A‐‐L. Using the hemolytic PFC technique low numbers of antibody‐producing cells were detected in spleens of C3H/HeJ mice. However, the avidity of these antibodies as measured by inhibition of PFC was low as compared with that observed for antibody produced in C3H.SW mice in response to the ordered (Tyr‐Tyr‐Glu‐Glu)‐A‐‐L. Genetic analysis experiments demonstrated a close linkage between the ability to respond to (Tyr‐Tyr‐Glu‐Glu)‐A‐‐L and the major histocompatibility locus (H‐2) of the mouse as was previously shown for (T, G)‐A‐‐L. In contrast, no linkage was observed between the immune response potential to (Tyr‐Glu‐Tyr‐Glu)‐A‐‐L and the H‐2 as indicated by the pattern of response of different inbred and congenic mouse strains and by genetic analysis.

Thus, the change in the order of two amino acid residues within the sequence of the tetrapeptide caused an enormous change in the biological specificity of the antibodies produced and in the genetic control of the immune response.
Membrane Ig on MPC11 myeloma cells: correlation between the expression of membrane Ig, a receptor for Ig and the process of secretion
Authors: Corte G. , Risso Angela , Ferrarini M. , Bargellesi A.
Published: February 2007

The expression of membrane immunoglobulin (mIg) was examined in three cloned MPC11‐derived mouse myelom a cell lines. Membrane immunofluorescence studies demonstrated that IgG2b producer cells (P1) had complete IgG molecules, L‐chain producer (L1) had only L‐chain determinants and nonproducer (NP2) did not have any Ig determinants on the cell surface.

An Ig receptor, with characteristics different from B lymphocyte Fc receptor, has been found to be present on secreting cells (P1 or L1), but not on the NP2 cell variant.

The data reported in the present paper indicate that the expression of mIg and of the Ig receptor molecule is clearly correlated with the process of secretion. In the light of previous data reported on Ig secretion, a model is proposed which correlates the process of secretion with the expression not only of mIg, but also of the receptor for Ig.
IgG response in vitro. I. The requirement for an intermediate responsive cell type
Authors: North J. R. , Askonas Brigitte A.
Published: February 2007

We have studied a secondary IgG anti‐dinitrophenyl response in dissociated mouse spleen cell cultures which is comparable in magnitude to the responses detected after adoptive transfer. The data indicate that the responsive precursor cell is not a recirculating memory cell but is an intermediate B cell type which appears in vivo after antigen challenge of primed mice. Both antigen and T helper cells are required for in vitro stimulation of the intermediate cell type into the division and maturation steps leading to IgG antibody secretion. The buoyant density of precursor cells has been analyzed by bovine serum albumin density gradient centrifugation, and is consistent with their recent origin by division from memory cells.
The lethal hit stage of mouse T and non‐T cell‐mediated cytolysis: differences in cation requirements and characterization of an analytical “cation pulse” method
Authors: Golstein P. , Smith E. T.
Published: February 2007

We investigated in detail the cation requirements of two different systems of mouse cell‐mediated cytolysis in vitro, at their recognition, post‐recognition hit and target cell disintegration stages. In T cell‐mediated cytolysis, respectively Mg++ or Ca++, Ca++, and no cations, were required. In non‐T cell‐mediated hemolysis, respectively no cations, Mg++, and no cations, were required. Two main conclusions can be drawn. First, the cation requirements are different from one system to the other especially at the post‐recognition hit stage, which strongly suggests the existence of differences between both systems as to the actual mechanism of lysis. Second, the cation requirements are different within each system from one step to another. This formed the basis of a step‐by‐step analysis of the lytic process, leading to the characterization of a cation pulse method for the experimental isolation and further study of the post‐recognition hit stage of cell‐mediated cytolysis.
Interaction of human lymphocytes with fluid phase human C3b detected by immunofluorescence
Authors: Simonian S. , Molenaar J. L. , Zeijlemaker W. P. , Knape J. T. A. , Bakker S. , Pondman K. W.
Published: February 2007

Human lymphocytes obtained from tonsils and peripheral blood were found to bind human fluid phase C3b, obtained by trypsin treatment. This binding was detected by indirect immunofluorescence (IIF) using specific anti‐C3 antisera. Lymphocytes isolated from thymus tissue scored low percentages in IIF, indicating that the main population of thymus‐derived lymphocytes are T cells.

The distribution pattern of C3b‐binding cells was compared with that of cells forming rosettes with sheep erythrocytes coated with antibody and complement (EAC) and with sheep erythrocytes (E) only, as well as with that of Ig‐ bearing lymphocytes, as detected by direct immunofluorescence. It appeared that the distribution pattern of lymphocytes which can bind fluid phase C3b is similar to that of EAC rosette‐forming and of Ig‐bearing lymphocytes. Pre‐ incubation of the lymphocytes with C3b and pretreatment of the cells with trypsin decreased the capacity to form rosettes and to bind C3b to their sur‐ face. Human monocytes, granulocytes and erythrocytes did not bind fluid phase C3b, as judged by IIF. Therefore, the selective binding of fluid phase C3b to lymphocytes provides a specific method for the detection of complement‐reactive lymphocytes in lymphoid cell preparations.
Immature T lineage lymphocytes in athymic mice Presence of TL, lifespan and homeostatic regulation
Authors: Roelants G. E. , Mayor Kathleen S. , Hägg Lena‐Britt , Loor F.
Published: February 2007

Lymphocytes belonging to the T lineage were described in athymic nude mice. We showed previously that they were distinguished from usual peripheral lymphocytes by their low density of Θ antigen, their slow electrophoretic mobility and their absence of recirculation through the thoracic duct. We now report that they also express the TL antigen, have a life span of 1 to 2 days, are produced in the bone marrow and are under the homeostatic influence of the thymus. Indeed they appear rapidly in surgically T‐deprived mice and their production is blocked in both surgically or congenitally athymic mice receiving a thymus graft. This homeostatic control may be mediated via a humoral factor. Cells with similar characteristics are present in the thymus at early stages of embryogenesis.

The characteristics of these T lineage lymphocytes strongly suggest that they may represent “pre‐thymocytes”, i.e. cells already committed to the T pathway independently of thymic influence but needing the thymus microenvironment to differentiate further.
Concentrations of three hapten‐binding immunoglobulins in pooled normal human serum
Authors: Karjalaninen K. , Mäkelä O.
Published: February 2007

The amount of natural anti‐DNP‐cap, anti‐NIP‐cap or anti‐ABA‐TYR in human IgM was measured by using immunoabsorbents and hapten elution. We found that 1.0 % of pooled human IgM is specific for DNP‐cap, 0.2 % for NIP‐cap and 0.02 % for ABA‐TYR. Haptens NIP and DNP were found to be cross‐reactive when tested with natural antibodies even though they were not cross‐reactive when tested with immune antibodies.
Studies on the lymphocytes of sheep. II. Some properties of cells in various compartments of the recirculating lymphocyte pool
Authors: Scollay R. , Hall J. , Orlans Eva
Published: February 2007

The proportion of cells bearing surface immunoglobulin (Ig) and the normal lymphocyte transfer (NLT) reactivity of mononuclear cells obtained from the blood, afferent lymph, and efferent lymph from both somatic and intestinal nodes of sheep were measured.

The proportion of Ig‐positive lymphocytes was approximately 30 5% in blood and efferent lymph, but only about 10% in afferent lymph. The proportion of unlabeled lymphocytes (T cells) was about the same in all the preparations, as afferent lymph contains 15–20% macrophages. Despite this apparent uniformity in the T cell content, the NLT reactivity of efferent lymph was 3 to 5 times higher than that of blood or afferent lymph. No humoral factors could be detected by incubating cells in the various plasmas in vitro before injection. No inhibitory cells could be detected when mixtures of cell populations were used to initiate lesions.

We suggest that lymphocytes in efferent lymph are more reactive than others because they are “groomed” by macrophages during their recirculatory passage through the substance of the node.
Suppressor cells in rabbit peripheral blood
Authors: Luzzati Alma L. , Lafleur L.
Published: February 2007

Rabbit peripheral blood leukocytes (PBL) added to cultures of autologous spleen cells, primed in vivo to sheep red cells, are able to suppress with high efficacy the secondary in vitro response of the spleen cells to that antigen. Removal of nylon wool adherent cells from PBL abolishes the suppressive effect. When the PBL are fractionated by velocity sedimentation the suppressor cells can be separated from the responding cells.

The circulating lymphocytes, freed from the inhibiting effect, either by nylon wool absorption or by velocity sedimentation fractionation, are able to give a strong secondary in vitro anti‐SRC response, in which the long latency period, usually observed when PBL are stimulated with antigen in culture, is abolished or at least reduced. The suppressor effect present in the PBL is not due to granulocytes, platelets or erythrocytes.
Cellular responses to murine alloantigens of the major histocompatibility complex. The role of cell subpopulations that express different quantities of H‐2‐associated antigenic markers
Authors: Plate Janet M. D.
Published: February 2007

Subsets of lymphoid cells that function in the initiation and differentiation of cell‐mediated responses to H‐2‐coded alloantigens were defined with an antiserum raised between congenic resistant lines of mice that differed for a limited number of components of the H‐2 complex.

Only those cells that express “Ia markers” can stimulate responses to H‐2K, D and/or I region antigens in mixed lymphoid cell cultures, even though all lymphoid cells apparently express the H‐2K and H‐2D‐coded private antigens. Ia markers, therefore, serve to distinguish the subset of cells which includes as its members the stimulating cells.

The Ia marker(s) is expressed on the cell membrane of at least one of the two T cell subsets that collaborate in the development of T effector cells to H‐2‐ associated alloantigens, i.e. precursors and helpers. The cells remaining after lysis with our antiserum plus complement no longer can respond in the MLR. Syngeneic non‐T cells cannot reconstitute the response.

Most activated and proliferating cells express the Ia determinant(s). A proportion of T effector or killer cells, however, does not express the Ia markers. We suggest, therefore, that the MLR‐responsive cell in normal lymph nodes is an “activated” cell and the “Ia markers” are involved in the differentiation of T precursor to T effector cells. The end stage T effector probably is devoid of the Ia marker.
Immune response region‐associated antigens of the mouse. Biochemical properties of detergent and papain solubilized molecules
Authors: Hess M.
Published: February 2007

Immune response region‐associated (Ia) antigens and classical H‐2 antigens are glycoproteins which differ in their molecular weight and tissue distribution. Ia and H‐2 molecules also show differences in overall charge, apparent isoelectric point and susceptibility to proteolytic degradation, acid treatment and exposure to 56°C. In the present paper, Ia.11d antigens were shown to have a molecular weight of about 35 000 after solubilization with non‐ ionic detergents. Purified Iad antigens, solubilized by controlled papain digestion, display a molecular weight of about 26 000 after final purification by indirect immune coprecipitation. This figure corresponds to the molecular weight of a highly purified H‐2 polypeptide fragment obtained after papain solubilization. The remarkable size similarity of proteolytic fragments from Ia and H‐2 antigens could suggest that these genetically and functionally related molecules possess some structural features in common.
Lymphocyte stimulation by protein A of Staphylococcus aureus
Authors: Forsgren A. , Svedjelund A. , Wigzell H.
Published: February 2007

Protein A from Staphylococcus aureus (SpA) is known to bind to the Fc region of most mammalian IgG classes. In the present article data are presented showing that SpA is a highly efficient mitogen for human peripheral B lymphocytes, with no detectable activity for T lymphocytes. In order to achieve optimal stimulating conditions SpA should be presented to the lymphocytes on an insoluble matrix, such as the SpA‐positive bacteria themselves or SpA covalently attached to Sephadex or Sepharose beads. Using such conditions SpA is equivalent with regard to stimulatory capacity for B lymphocytes as phytohemagglutinin is for the human T lymphocytes. Specificity controls proved beyond doubt that SpA and not any other contaminating product is the B cell mitogen.

It is concluded that SpA as an inducer of human B lymphocyte division might serve as a highly useful assay in the clinical assessment of B lymphocyte function. It should also be a suitable tool in the fine analysis of B lymphocyte activation via the specific interactions with surface IgG molecules.
Studies on the activation of mouse bone marrow‐derived macrophages by the macrophage cytotoxicity factor (MCF)
Authors: Meerpohl H.‐G. , Lohmann‐Matthes Marie‐Luise , Fischer H.
Published: February 2007

The capacity of bone marrow‐derived macrophages to be rendered cytotoxic by macrophage cytotoxicity factor (MCF) at different stages of maturation was tested. Under in vitro conditions not only mature macrophages but also nonadherent precursor cells were successfully activated. Mature adherent bone marrow macrophages can be rendered cytotoxic for up to three weeks in tissue culture. Cytotoxic effects are demonstrable even at a killer target ratio of 0.5: 1. Granulocytes do not respond to activation with MCF. Bone marrow‐derived macrophages can be collected at early stages of maturation, when they grow in suspension or have developed only loose adherence. Macrophages which have differentiated in vitro from bone marrow never show any signs of nonspecific activation as measured by our cytotoxic assay system.
Stimulation of lymphocytes by allogeneic lymphocytes and lymphoblasts in the presence of anti‐HLA antisera
Authors: Corley R. B. , Dawson J. R. , Amos D. B.
Published: February 2007

Anti‐HLA alloantisera inhibit mixed lymphocyte responses in which normal lymphocytes are used as stimulator cells. These same antisera are unable to inhibit lymphocyte proliferative responses stimulated by lymphoblastoid cells from cultured lymphoid cell lines. They also fail to inhibit either the generation of cytotoxic effector cells by lymphoblastoid cells or lymphocyte‐mediated cytotoxicity against the lymphoblasts. Although the number of HLA antigens on the surface of lymphoblasts is reported to be greater than on normal lymphocytes, the failure of alloantisera to inhibit lymphoblast‐induced responses in vitro does not appear to be due to insufficient amounts of antiserum to react with the antigenic sites. Rather, the data are interpreted to suggest that antigens which are not HLA and are not closely associated with HLA on the lymphocyte membrane are responsible for the stimulation of allogeneic lymphocytes by lymphoblastoid cells.

Although lymphoid cell lines are known to contain the genome of the Epstein‐Barr virus, antisera against products of the viral genome fail to inhibit proliferative responses to lymphoblastoid cells, suggesting that these antigens do not directly participate in lymphocyte activation.
Selective breeding of mice for antibody responsiveness to flagellar and somatic antigens of Salmonellae
Authors: Siqueira Maria , Bandieri A. , Reis Moema S. , Sant'anna O. A. , Biozzi G.
Published: February 2007

Selective breeding has been performed in mice for their high or low antibody responsiveness to Salmonella antigens (Ag). Two noncross‐reacting Salmonellae (S. typhimurium and S. oranienburg) have been alternately used to immunize successive generations in order to avoid interference of maternally transmitted antibody. Both Salmonellae carry two independent antigens: flagellar (f) and somatic (s). Two two‐way selections were carried out: one for agglutinin response to fAg and the other for agglutinin response to sAg (Selection Ags). The agglutinin response to the other independent Ag was also measured (Associated Ags). The phenotypic character chosen for selection is the maximal agglutinin titer in response to optimal immunization.

In both selections, high and low responder lines diverged progressively. There was a 27‐fold interline difference in the F13 generation of selection for fAg response and a 38‐fold one in the F11 generation of selection for sAg response. This divergence and the continuous distribution of phenotypes in the foundation population indicate that the quantitative character investigated is subject to polygenic regulation. The realized heritability (h2) of the character, measured from the interline divergence, was 0.18 ± 0.06 in both f and s selections. This means that about 20 % of the phenotypic variance of the foundation population is additive.

The modification of immune responsiveness to the selection Ag produced by selective breeding was accompanied by a parallel and equivalent effect on immune responsiveness to the noncross‐reacting Associated Ag. This effect is therefore entirely nonspecific. A small but definite sex effect in favor of female antibody responsiveness was demonstrated.

The results are discussed in comparison with other selection experiments made in mice for quantitative antibody response to other antigens.
Control mechanism of lymphocyte traffic. Altered distribution of 51Cr‐labeled mouse lymph node cells pretreated in vitro with lipopolysaccharide
Authors: Freitas A. A. , de Sousa Maria
Published: February 2007

The effect of in vitro treatment of mouse lymph node cell populations with lipopolysaccharide (LPS) on their migration in syngeneic recipients was studied.

LPS‐exposed cells had a decreased lymph node localization and an increased spleen distribution when compared to control untreated cells, after intravenous injection into syngeneic recipients. This effect of LPS on cell traffic was maximal at 24 h and could not be detected at either 1 or 72 h after cell transfer.

These changes induced on cell distribution by LPS treatment are interpreted as the consequence of a modified interaction between the circulating lymphocytes and the resident cells within the spleen of the recipients.
The antigen‐inexperienced thymic suppressor cells: a class of lymphocytes in the young chicken thymus that inhibits antibody production and cell‐mediated immune responses
Authors: Droege W.
Published: February 2007

Transfer of thymus cells from young chickens in combination with a light whole body irradiation (360 R) was found to suppress the rejection of skin grafts across strong histocompatibility (B) differences. On the average, the suppressed animals also showed decreased serum hemagglutinin titers against erythrocytes of the skin donor strain and a decreased graft‐versus‐host (GvH) reactivity against embryos of this strain.

The thymic suppressor cells can be obtained from animals that have not experienced the antigen under test. However, after transfer and contact to the antigen (skin graft) they can lead to the formation of specific (“activated”) suppressor cells and can mediate in the long run a specific inhibition of the response to this antigen.

The suppressive activity is associated with a bursa‐dependent cellular subpopulation in the thymus that is different from B lymphocytes, B precursor cells or GvH‐reactive T cells. The bursa dependency of the thymic suppressor cell suggests that functionally different lineages of thymic and thymus‐derived lymphocytes are derived from different sources of prethymic stem cells. The suppressor cells are predominantly found in the young chicken thymus and already detectable in the 16‐day‐old embryo, while poor suppressive activity is found in the adult thymus.

The suppressive effect can be obtained with thymus cells from either syngeneic or allogeneic donors. Embryonic allogeneic donors provide suppressive cell preparations free of GvH reactivity.

The possibility that the thymus suppressor cells mediate self tolerance and “neonatal tolerance” is discussed.
Fusion between immunoglobulin‐secreting and nonsecreting myeloma cell lines
Authors: Köhler G. , Howe S. C. , Milstein C.
Published: February 2007

The defects in two nonsecreting variant clones of the mouse plasmacytoma MOPC 21 (P3) were studied by tissue culture methods. The variants (NSI and NSIII) do not synthesize detectable heavy chains. NSI synthesizes, but does not secrete, light chains and NSIII does not synthesize light chain.

A screening procedure was used allowing the detection of revertant cells secreting immunoglobulin. The method is based on a hemolytic plaque assay using anti‐immunoglobulin‐coated red cells. No revertants were detected among 2 × 107 cells. Both variant lines were fused to another myeloma line (PI) which secretes a complete immunoglobulin and excess light chains. Analysis of the products by isoelectric focusing showed that in the hybrids there was no reactivation of synthesis of the nonexpressed chains. The defects leading to loss of synthesis cannot therefore be complemented in the hybrid lines.

The secretion of light chain in NSI, on the other hand, could be complemented in the hybrid but the light chain was only secreted as part of a new immunoglobulin hybrid molecule.
B cell tolerance induced by polymeric antigens V. Different avidities of primed and virgin precursor cells for paucivalent antigen
Authors: Willcox H. N. A. , Klaus G. G. B.
Published: February 2007

We have compared the avidity of virgin and primed hapten‐specific precursor cells for DNP‐lys‐S3 (dinitrophenylated type 3 pneumococcal polysaccharide) by measuring its capacity to prevent them from binding highly radioactive DNP‐hemocyanin, and thereby protect them from committing hapten‐specific “suicide”.

Moderately substituted conjugates (e.g. DNP‐2.7S3) protected virgin and memory B cells impartially. In contrast, DNP‐lyso0.6S3 protected memory cells efficiently, but protected virgin cells only at considerably higher concentrations.

These results are consistent with previous evidence – from this and other systems – that there is a higher density of receptors on primed than on unprimed B cells – the significance of which is discussed.
Inheritance of antibody specificity. The IgM anti‐lipopolysaccharide response in mice
Authors: Pauli R. Di
Published: February 2007

Mice of different genotypes were immunized with Salmonella anatum. The cross‐reactivity patterns of their IgM anti‐S. anatum lipopolysaccharide (LPSAN) antibodies were characterized by their relative avidity toward heterologous LPS.

When the LPS from S. cholera suis (LPSCHS) was used as the heterologous LPS, clear differences between mouse strains were found. DBA/2 and DBA/1 showed cross‐reacting IgM, whereas C57BL/10, C57BL/6, BALB/c‐Igb and B10.D2 had mainly noncross‐reacting IgM. In C3H and C57BL/6‐Iga, individual mice express either the cross‐reacting or the noncross‐reacting antibodies.

The IgM antibodies from individual mice were further characterized for their cross‐reactivity toward the LPS from S. strasbourg (LPSSTR) and S. illinois (LPSILL). Only individual patterns with no correlation to the cross‐reactivity pattern with LPSCHS were found. This shows that more than one antibody type is characterized by cross‐reactivity.

(B 10.D2 × DBA/1)F1 mice showed a biphasic distribution of cross‐reactivity. Of the F1 x DBA backcross mice 21 % had IgM antibodies which showed no cross‐reaction with LPSCHS. This still is in agreement with one locus controlling this phenotype.

This locus segregates independently from Ig allotype since no correlation was found between allotype and cross‐reactivity pattern in F1 x DBA backcross mice.
The immunological properties of haptens coupled to thymus‐independent carrier molecules. IV. The IgG response to dinitrophenylated Ficoll
Authors: Klaus G. G. B. , Phillips Jennifer M. , Humphrey J. H. , Dresser D. W. , Cross Anne M.
Published: February 2007

Dinitrophenylated polysucrose (DNP‐Ficoll) elicits T cell‐independent IgM anti‐DNP antibody formation in mice. This antigen also elicits a heterogeneous IgG1 and IgG2 anti‐DNP response, which is operationally as T‐independent as the IgM response. However, a concomitant graft‐versus‐host reaction markedly enhances the IgG response (allogeneic effect). These results confirm those of others, indicating that a certain proportion of the precursors of IgG‐producing cells can be triggered by some T‐independent antigens. However, our results suggest that even with such antigens optimal triggering of IgG precursors requires T cell help.
Demonstration that IgG memory is carried by IgG‐bearing cells
Authors: Okumura K. , Julius M. H. , Tsu Theta , Herzenberg Leonore A. , Herzenberg L. A.
Published: February 2007

Memory B cells which give rise to JgG antibody‐producing cells were generally assumed to be IgG‐bearing cells. However, recent studies indicating that very few IgG‐bearing cells exist in lymphoid tissue brought this assumption into question. In this study, we examined directly the question whether IgG‐bearing cells contain functional precursors of IgG antibody‐producing cells. Using the adoptive secondary immune response, we demonstrated that Ig‐1b‐bearing cells, isolated with the fluorescence‐activated cell sorter (FACS), are the functional precursors of Ig‐1b‐producing cells. Further, we have enriched IgG2 and IgG1 memory B cells using the FACS. The results show that IgG2‐bearing cells are the functional precursors of the IgG2 antibody‐producing cells. Likewise, the IgG1‐bearing cells are the functional precursors of IgG1 antibody‐producing cells. Thus, IgG memory cells have surface IgG which indicates the class and allotype commitment of the memory cell and its progeny antibody‐forming cells.
Effect of anti‐carrier antibody on carrier‐determined tolerance
Authors: Terres G. , Aldo‐Benson Marlene , Borel Y.
Published: February 2007

These experiments were originally designed to determine whether an anti‐carrier antibody, e.g., anti‐allotype could break hapten‐specific tolerance in vivo. Tolerance to 2,4‐dinitrophenyl (DNP) was induced in C57BL/6J mice using DNP‐BALB/c IgG2a conjugate. When anti‐allotype serum was injected in C57BL/6J mice one day after a single injection of DNP‐IgG2a the mice were not tolerant. In contrast, when tolerance was induced by four weekly injections of tolerogen, the anti‐allotype serum had no effect on the tolerant state. This effect was specific for tolerance‐inducing carrier.

Anti‐carrier antibody injected in C57BL/6J mice one day after DNP‐IgG2a produced a small but significant anti‐DNP response without administration of the immunogen, whereas the tolerogen (DNP‐IgG2a) by itself was not immunogenic. Similarly, despite multiple injections of DNP‐IgG2a, bearing the foreign allotype, only one out of 7 C57BL/6J mice showed a weak anticarrier response. In contrast, a marked anti‐carrier (IgG2a) response was obtained when the anti‐allotype antibody was passively administered in C57BL/6J mice.

In conclusion, these experiments suggest that tolerance to an antigenic determinant may be broken by an antibody directed not to this determinant, but to another on the same molecule. The significance of this finding in relationship to the mechanism of the carrier‐determined tolerance and the breakdown of self‐tolerance is discussed.
Human T cell receptor for IgM: specificity for the pentameric Fc fragment
Authors: Ferrarini M. , Moretta L. , Mingari Maria C. , Tonda P. , Pernis B.
Published: February 2007

The specificity of the IgM receptor expressed by human T cells cultured in IgM‐free media has been investigated. IgM receptors have been detected using a rosette system with ox erythrocytes coated with rabbit antibody (EA(IgM)), and the inhibitory capacity of different IgM fragments in the rosette system has been tested. It was found that F(c)5μ but not F(ab′)2μ, nor monomeric IgM (8 S IgM) inhibited EA(IgM) rosette‐forming cells. This indicates that the receptor present on the surface of T cells has affinity for a structure located in the Fc portion of the pentameric IgM.
Specific enrichment of antigen‐binding receptors from sensitized murine lymphocytes
Authors: Krawinkel U. , Rajewsky K.
Published: February 2007

Splenic T and B lymphocytes from sensitized mice were adsorbed to antigen‐coated nylon discs and released from the discs by temperature shift as described by Kiefer, H., (Eur. J. Immunol. 1973. 3: 181 and 1975. 5: 624). After cell release, lymphocyte‐derived antigen‐binding material could be recovered from the discs. A major fraction of the activity (70–80%) binds to anti‐immunoglobulin immunosorbents. A minor fraction does not detectably cross‐react with γ, μ, α and k immunoglobulin poly‐peptide chains. When filtrated through Sephadex G‐200, the bulk of activity of both fractions elutes in the region of 7 S serum antibody. However, as demonstrated for (4hydroxy‐3‐nitro‐phenyl)acetyl (NP)‐binding material from C57BL/6 lymphocytes, the average affinity for antigen of the two fractions is drastically lower than that of humoral antibody, and the average affinity of the minor fraction is lower than that of the major fraction.

The fraction of lymphocyte‐derived antigen‐binding material that does not adsorb to insolubilized anti‐immunoglobulin serum was found to be proportional to the fraction of T lymphocytes in the input cell population and may therefore represent antigen‐binding T lymphocyte surface receptors.
Genetic control of the immune response to the radom linear terpolymer of L‐glutamic acid, L‐lysine and L‐leucine (GLleu) by complementing Ir genes
Authors: Dorf M. E. , Twigg Martha B. , Benacerraf B.
Published: February 2007

Three levels of humoral responsiveness (none, high or marginal) were noted following secondary immunization with the random linear terpolymer of L‐glutamic acid, L‐lysine and L‐leucine (GLleu). These immune responses were under dual H‐2‐linked Ir gene control. Gene complementation was observed in appropriate F1 offspring between two nonresponder strains and in selected intra‐I region recombinants derived from crossing over between nonresponder parental haplotypes. One of the Ir‐GLleu genes, β, was localized within the I‐A or I‐B subregions. The other Ir‐GLleu locus, termed a, was mapped in the I‐C or S subregions. Differences in the strain distribution of immune responsiveness to GLleu and a related terpolymer GLphe (which is also under complementing Ir gene control) are primarily attributable to differences among the Ir‐GLleu and Er‐GLphe β alleles. A correlation exists between the presence of the Ir‐GLleu α(+)allele and the gene coding for specificity Ia.7.
Rabbit antibody light chains: selective breeding narrows variability in framework and complementarity‐determining residues
Authors: Braun D. G. , Huser H. , Riesen W. F.
Published: February 2007

The amino acid sequence of 5 light (L) chain (b4)variable (VL) regions and the partial sequence of VL (K) regions from 12 anti‐streptococcal group A‐variant polysaccharide (Av‐CHO) and 2 anti‐streptococcal group C polysaccharide (C‐CHO) antibodies was determined. These sequences contain 70 invariant positions as opposed to 50 invariant positions in other rabbit VL regions. Variability within the framework residues lacks randomness, and parent offspring relationship or otherwise close familial relationship is apparent in several instances. Variability in the complementarity‐determining regions is reduced by 2.3–5.5‐fold in comparison with other rabbit L‐chains with several identical first and third hypervariable regions. Residue positions 50‐56, known to mark the second hypervariable region in human K‐chains, are not hypervariable in L‐chains from Av‐CHO rabbit antibodies. Considering the 67 rabbit L‐chain sequences, completely or partially known today, for counting the number of V region germ line genes, it is concluded that the species rabbit has at least 27 VL germ line genes available.
Immunosuppressive activity of submaxillary gland extracts of the mouse 1. Effect on antibody formation in response to sheep red blood cells
Authors: Koch Judith H. , Rowe Janet
Published: February 2007

Aqueous extracts of mouse submaxillary glands yield six peaks on Sephadex G‐75 columns, each containing several molecular species. Two of these fractions (III and IV) have a profound effect on the immune response.

When given a day before immunization with sheep erythrocytes, the number of antibody‐producing cells is reduced ten‐fold or more, and the switch from IgM to IgG is virtually absent. Administration two days before or on the day of immunization results in about 50 % depression; outside this range there is no effect.

The dose‐response curve is of sigmoidshape, with the median at about 0.5 mg of fraction III/40 g mouse, reaching an asymptote after doses of ⩾ 5 mg at about 5 % of the response of untreated mice.

Depression of the primary response does not prevent the development of immunological memory: the secondary response is typical in the early and predominant appearance of IgG‐producing cells, although their numbers are somewhat lower than in the controls which received no treatment before primary immunization. Treatment on the day before boosting abrogates the secondary response.

The immunotranquillizer from mouse submaxillary glands acts equally well on syngeneic and allogeneic recipients, affecting the earliest stage of the immune response. The results are compatible with the induction of a temporary block in the development of helper T cells.
A plaque assay for all cells secreting Ig of a given type or class
Authors: Gronowicz Eva , Coutinho A. , Melchers F.
Published: February 2007

A modification of the hemolytic plaque assay using protein A‐coated red cells is described which makes use of the fact that the Fc portion of IgG binds to protein A. A number of murine plasmacytomas secreting different classes of Ig have been tested for plaque formation with these indicator red cells. In the presence of complement‐binding antibodies specific for the corresponding class of secreted Ig, between 10 and 70 % of all plated myeloma cells formed plaques. The assay shows a prozone effect in excess of antibody, suggesting that complexes of antibody and secreted Ig effect lysis of the target cells. This assay can be used to enumerate cells secreting any molecules for which complement‐binding antibodies are available.
Generation of cytotoxic cells in absence of blastogenesis by mouse leukemic cells in mixed cultures
Authors: Collavo D. , Biasi G. , Colombatti A. , Chieco‐Bianchi L.
Published: February 2007

Primary virus‐induced murine leukemias and transplantable leukemic cell lines, originally induced by virus, chemical or physical agents, failed to stimulate normal spleen cells differing at the H‐2 complex or at M1s locus in the one‐way mixed leukocyte culture. Lack of stimulation seems at least partially due to a nonspecific inhibitory effect since in a “three‐party” culture system the leukemic cells interfered with the mixed leukocyte reaction (MLR) of normal allogeneic cells. Characterization of the leukemic cell populations used, according to their T or B cell origin, disclosed that in most cases T cell markers were present. Also, no Ia antigens were detected on leukemic cells. Furthermore, using a 51Cr release assay, leukemic cells could sensitize allogeneic normal lymphocytes to kill specifically normal as well as leukemic targets, even when no MLR was detected in parallel cultures.
Structural aspects of immune recognition of lysozymes. III. T cell specificity restriction and its consequences for antibody specificity
Authors: Cecka J. M. , Stratton J. A. , Miller A. , Sercarz E.
Published: February 2007

We have studied the relationship between the determinants encountered by T cells on an antigenic molecule and the specificities of the antibodies eventually produced by the B cells with which these T cells cooperate. The number of epitopes on the hen lysozyme (HEL) molecule available to T cell receptors was functionally limited by inducing T cell tolerance to HEL in rabbits. Highly cross‐reactive lysozymes were then used to challenge the HEL‐unresponsive rabbits. Only T cells which recognize new epitopes on the challenge lysozymes could act as helpers in generating an anti‐lysozyme response.

Amino acid differences between Japanese quail lysozyme (JEL) and HEL are segregated within a single quadrant of this small antigen molecule. HEL‐tolerant rabbits challenged with JEL produced antibodies which were totally cross‐reactive with the tolerogen HEL. This result is in contrast to the result obtained in nontolerant rabbits which produced antibodies to JEL which were only 50–70 % cross‐reactive with HEL. We conclude that T cells restricted to the JEL‐unique epitopes were only capable of cooperating with B cells specific for common epitopes shared between JEL and the tolerogen HEL. Turkey lysozyme (TEL), on the other hand, bears different amino acids which are distributed over several regions on the surface of the molecule. Any one HEL‐tolerant rabbit developed a restricted response to TEL; in some rabbits the anti‐TEL was highly HEL cross‐reactive, while in others little cross‐reactivity with HEL was observed. Each of four HEL‐tolerant rabbits injected with the minimally altered bob‐white quail lysozyme possessed the reactive T cells necessary to mount a limited response to this challenge lysozyme, suggesting a diverse library of T cell specificities. Recognition of the small differences between the challenge lysozymes and the tolerogen HEL required the T cells of these tolerant rabbits to make a fine discrimination between minimally changed epitopes.
Evidence for an absence of cross‐reactivity between human β ‐microglobulin and human IgG allotypes and subclasses
Authors: Colle A. , Tonnelle C. , Manuel Y. , Rivat L. , Ropartz C.
Published: February 2007

Six β‐microglobulins were isolated from the urine of six patients with renal tubular dysfunction. Cross‐reactivity between these β ‐microglobulins and antigenic determinants of different IgG allotypes and subclasses was investigated. No evidence of cross‐reactivity was found. Some hypotheses are discussed concerning these results.
Role of early viral surface antigens in cellular immune response to vaccinia virus
Authors: Koszinowski U. , Ertl Hildegund
Published: February 2007

Infection of mice with the vaccinia virus strain WR, Elstree or DIs, a conditional lethal mutant of vaccinia virus, resulted in the generation of vaccinia virus‐specific sensitized cytolytic T lymphocytes (CTL). It could be shown by cross‐reactivity between the three strains and by inhibition experiments with specific antisera that early vaccinia surface antigens are sufficient for the generation of specific CTL in vivo and for the lysis of infected target cells in vitro.