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Biomedical subjects

D Juy

Publications and source records attributed to D Juy.

At least 19 recordsLinked to original sources
PubMed1988

Murine anti-TNP antibodies positive for either lambda 1 or lambda 2 light chains express common idiotypic determinants.

Although the lambda-bearing antibodies represent only 5% of the total mouse serum immunoglobulins, some antigens such as B1355 dextran (alpha (1-3)Dex), the 4-hydroxy-3-nitrophenyl acetyl (NP) and 2,4-dinitro or 2,4,6-trinitrophenyl (DNP/TNP) antigens can induce lambda-positive immune responses. In contrast to the lambda antibody response against alpha (1-3)Dex and NP antigens which is restricted to the lambda 1 isotype it was shown that the response to the DNP (or TNP) antigen uses lambda 1 and lambda 2 and lambda 3 isotypes. The idiotypy of the alpha (1-3)Dex and NP systems has been well characterized contrary to that of the lambda-positive anti-TNP/DNP response which has been poorly studied. In this paper, we describe two idiotopes (Id C19-3 and Id D11-2) shared by two BALB/c monoclonal anti-TNP antibodies (TNP5 and TNP9) which, respectively, use the lambda 1 and lambda 2 light chains. These idiotopes were independently expressed on other monoclonal anti-TNP/DNP antibodies and appear to require the use of a unique VH gene associated with a particular V lambda region. After TNP-Ficoll immunization, BALB/c mice recurrently express both idiotopes on lambda 1 and (lambda 2 + lambda 3) anti-TNP antibodies. In addition, all the mouse strains immunized against TNP-Ficoll give a lambda 1- and (lambda 2 + lambda 3)-positive immune response with the exception of SJL and SJA strains which present a deficit for the expression of lambda 1 light chain. The expression of Id C19-3 was restricted to the strains with the Igh-Va allotypic haplotype (including SJA) whereas the Id D11-2 was extensively expressed in the various strains.

Animals↗
PubMed1987

Autoreactive T cell clones of MHC class II specificities are produced during responses against foreign antigens in man.

Although the existence of autoreactive T cells has been widely reported in mice and in guinea pigs, a similar phenomenon is poorly documented in man. Here we report the study of three human autoreactive T cell clones isolated during immunization of HLA-DRw13 donors either against influenza A/Texas virus or against allogeneic cells. These clones are specific for autologous HLA-class II specificities either common to all HLA-DRw13 molecules or restricted to the HLA-DR products specific for the DW19 subtype of HLA-DRw13. They are also cytotoxic and they have the same specificity when tested for lytic activity or in proliferation assays. Furthermore, they are also able to help autologous B cells to polyclonally produce Ig. The possible implication of such clones in regulatory mechanisms involving HLA-class II molecules is discussed.

Adult↗
PubMed1987

Idiotypic characteristics of lambda 1-bearing anti-alpha(1----3)dextran response in wild mice: high frequency of responder strains and co-expression of IdI 558 and IdI 104 on the same molecule.

In laboratory mouse strains, only mice with the IghCa phenotype are able to mount an immune response against the alpha(1----3) glycosidic linkage of the B1355 dextran. The response is highly restricted with respect to utilization of only V lambda 1 and few related members of the VH558 family, and characterized by the production of cross-reacting (IdX), and individual (IdI) 104 and 558 idiotopes. We report in this study data showing a large degree of polymorphism in the anti-alpha(1----3)Dex response among 35 wild-derived mouse strains belonging to 4 different species. In contrast to the anti-alpha(1----3)Dex response of common laboratory strains, neither this response nor expression of the IdX, and IdI 104 and 558 idiotopes are linked to the IghCa haplotype. We also demonstrate co-expression on the same molecule of IdI 104 and IdI 558 idiotopes in wild mouse-derived hybridomas. These data challenge the idea of the exclusive expression at the molecular level of IdI 104 or IdI 558.

Animals↗
PubMed1987

Frequency analysis of human peripheral blood B cells sensitive to CD2 monoclonal antibody-activated T cells.

Recent studies have demonstrated that appropriate pairs of cluster of differentiation 2 (CD2) monoclonal antibodies (MoAbs) directed against two epitopes on the T11 molecule induced human T-cell activation leading to the production of several lymphokines. Here we report that human peripheral blood B lymphocytes cultured in the presence of the CD2 (D66 + T11) MoAb, together with T lymphocytes and monocytes, secreted larger amount of immunoglobulin (Ig) than when they were incubated in the same culture conditions in the presence of pokeweed mitogen (PWM). We further show that the level of Ig secreted by the progeny of a single responsive B cell is similar in both systems and demonstrate that the increase in the Ig concentration is directly related to the high frequency of B-cell precursors sensitive to CD2 MoAb-activated T cells.

Antibodies, Monoclonal↗
PubMed1985

Igh restriction of the anti-alpha (1-3) dextran response: polyclonal B cell activators induce the synthesis of anti-alpha (1-3) dextran antibodies in lymphocytes from Igha mice only.

The only strains of mice which are able to synthesize lambda 1-bearing antibodies in response to alpha (1-3) Dextran are those expressing the Igha allotypic haplotype or those having an Igh V region identical to Igha mice. The experiments reported here were designed to investigate whether the nonresponsiveness of mice which do not express the Igha haplotype is a consequence of an absence of a polyclonal B cell receptor for the alpha (1-3) Dextran TI-antigen. B cells of several mouse strains were stimulated with polyclonal B cell activators (PBA) known to either stimulate non-overlapping B cell subsets or to stimulate B cells at different stages of maturation, i.e., lipopolysaccharide, Nocardia delipidated cell mitogens and alloreactive T helper cells. Whereas all three PBA induced B cells from Igha mice to secrete lambda 1-bearing anti-alpha (1-3) antibodies, the PBA were incapable of inducing B cells from non-Igha mice to mount an anti-alpha (1-3) Dextran response. The data suggest that non-Igha mice lack a functional VH Dex gene for the lambda 1-bearing anti-alpha (1-3) Dextran response.

Animals↗
PubMed1983

The selection and maintenance of the V region determinant repertoire is germ-line encoded and T cell-independent.

The number of lipopolysaccharide-sensitive precursor cells synthesizing immunoglobulin (Ig) which reacts with the monoclonal anti-M460 antibody F6(51) has been determined in the spleen and in the bone marrow of different strains of mice. These precursor frequencies fall into two quantitatively different groups. The first group includes mice with the same Igh haplotype as BALB/c animals (Igha). In this group, spleen cells contained between 1:10(4) to 1:5 X 10(4) B cell precursors secreting Ig which bound F6(51). The second level of precursor was obtained with animals with allotypic haplotypes other than Igha. These values were too low to allow accurate frequency determinations. The frequency of these cells in mice of the latter group, however, increased dramatically when these animals were hyperimmunized with the monoclonal anti-M460 antibody. Similar results were obtained when the frequencies were determined using the Ig- fraction of bone marrow cells. Surprisingly, the numbers of lipopolysaccharide-sensitive B cell precursors secreting F6(51)-binding Ig in spleen cells of nude mice was found to be similar to the one in splenocytes of normal mice, and even in this case, the frequencies reflected the genetic background of the animals tested. Taken together these data support the notion that the establishment and the maintenance of the M460 idiotypic repertoire is germ-line encoded and independent of regulatory T cells.

Animals↗
PubMed1983

Allotypic restriction of the expression of MOPC460 idiotope after immunization with either anti-2,4-dinitrophenyl (DNP) or anti-idiotypic antibodies.

The MOPC460 idiotype is expressed in mice with the IghCa allotypic haplotype after anti-2,4-dinitrophenyl (DNP) immunization. We have previously shown that two monoclonal syngeneic anti-idiotypic antibodies (IDM 92-13 and IDM 41-27) define two distinct idiotopes (the 460.92 and the 460.41) on the M460 idiotype. The current study demonstrates that only one idiotope (460.92) is recurrently expressed after antigen immunization in IghCa positive mice and also that, immunization against the monoclonal anti-idiotypic molecules induces the synthesis of 460.92 idiotope positive anti-DNP antibodies. However, the detection of such molecules is only possible when animals with the IghCa allotypic haplotype are immunized with the IDM 92-13 molecules. Immunization of mice with either of the two monoclonal anti-idiotypic antibodies never results in the synthesis 460.41 positive molecules. Therefore, whatever protocol of immunization used, the expression of 460.92 was allotypic restricted.

2,4-Dinitrophenol↗
PubMed1982

Idiotype regulation: evidence for the involvement of Igh-C-restricted T cells in the M-460 idiotype suppressive pathway.

Allotypic restriction of idiotype suppression has been shown in several idiotypic systems. It has also been demonstrated that naive BALB/c mice contain naturally occurring suppressor T cells capable of inhibiting the M-460 idiotype expressed on BALB/c B cells, and that T cells from allotype-congenic mice have no effect on this expression. Since we have previously shown that upon polyclonal activation B cells of all mice tested are capable of secreting M-460-positive anti-2,4,6-trinitrophenyl (TNP) antibodies, we postulated that idiotype suppressor cells may recognize idiotypes in conjugation with products of the Igh loci. In the present study we tested this hypothesis. The data clearly showed that regardless of their allotypic haplotype all strains of mice do possess suppressor cells capable of recognizing the M-460 idiotype. However, mixing experiments indicated that the functional potential of these suppressor cells can only be expressed when T and B lymphocytes come from allotype-matched animals. Efficient suppression in those cultures containing allotype-matched but incompatible B and T cells at the I-J region of the H-2 locus could be detected. Finally, using allotypic recombinant strains of mice, we found evidence that the restrictive elements in idiotypic suppression are the product of genes mapping in the Igh-C locus, or closely linked to it.

Animals↗
PubMed1982

A self determinant recognizing T cell hybridoma.

A T cell hybridoma (53(113)) obtained by fusion of BALB/c spleen cells and the BW 5147 lymphoma T cell line is described. This hybridoma recognizes mouse RBC (MRBC) and rat RBC, but not human, rabbit, guinea pig, or SRBC. The culture supernatant possesses hemagglutinating activity for the same indicator RBC. In addition to this, 53(113) cells are able to form protein A plaques in the presence of guinea pig complement and normal mouse serum (NMS) or purified mouse immunoglobulins (Ig). Because mouse Ig as well as sonicates from MRBC are able to inhibit the rosettes between the hybridoma cells and the MRBC, and because the sonicates inhibit protein A plaque formation, it seems likely that the same product can recognize a similar determinant expressed on MRBC and mouse Ig. The hypothesis that a 53(113) structure recognizes identical or cross-reactive carbohydrate determinants shared by murine Ig and C is considered.

Animals↗
PubMed1981

Induction and regulation of silent idiotype clones.

In order to study whether allotype linkage of idiotype expression is related to the total absence of structural gene(s) or to regulatory mechanisms acting on its phenotype expression, the M460 clone expression was followed in b cells from various inbred and recombinant strains of mice cultured at low density in the presence of lipopolysaccharide. Under these conditions, all cultures were found to contain anti-trinitrophenyl (TNP) antibody plaque-forming cells, some of which inhibitable by anti-M460 immunoglobulins. In the course of these studies, it also became apparent that, even in the absence of T cells, B lymphocytes are able to exert regulatory functions. Experiments carried out using anti-M460 hybrid cells F6(%!), and affinity-purified anti-(anti-M460) antibodies revealed that clonotype regulation by B cells is mediated by idiotype-auto-antiidiotype interactions.

Animals↗
PubMed1981

Recognition of MOPC-460 variable region determinants by polyclonally distributed triggering receptors on B lymphocytes.

Purified M460 protein-induced untreated and anti-Thy 1.2 and complement-treated murine spleen cells to proliferate and differentiate in vitro. Fc receptor complexing was not responsible for the phenomenon, since M460 Fab fragments retained the B cell triggering activity. Activation was inhibitable by the addition of DNP-glycine to cultures and could also be detected by using spleen cells from various strains of mice, including the C3H/HeJ, which is genetically nonresponding to LPS. Hybrid molecules were constructed between the M460 proteins and the products of 2 myelomas that do not activate B cells, namely, X25 and X24. The only hybrid molecules that retained triggering activity were (L460-Hx25)2. Interestingly, the same molecule was also the only one recognized by an anti-M460 monoclonal antibody (F6(51)) that has been previously shown to induce B cells to proliferate and differentiate. The data suggest the existence on B lymphocytes of a network of polyclonally distributed mitogen receptors that share determinants cross-reacting with immunoglobulin idiotypes.

Animals↗
PubMed1979

In vivo activation of murine peritoneal macrophages by Nocardia water soluble mitogen (NWSM).

In vitro NWSM has been shown to be a B cell mitogen and a polyclonal activator. Although NWSM has been also shown to be adjuvant active in vivo, motogenicity and polyclonal activation are not observed when this fraction has been administered to mice. In contrast, the experiments reported here demonstrate that after in vivo administration several effects of NWSM on mouse peritoneal macrophages can be observed: NWSM was able to induce an important increase in the ability of peritoneal macrophages to inhibit in vitro growth of tumor cells, to increase their phagocytic activity and to enhance their ability to induce an immune response, following the incubation with an antigen NWSM was able to stimulate phagocytic activity of macrophages of C3H/He Orl. mice (LPS-resistant strain). Those findings suggest that the adjuvant activity of NWSM in vivo can be related to its capacity to activate macrophages.

Adjuvants, Immunologic↗
PubMed1979

A new rapid rosette-forming cell micromethod for the detection of antibody-synthesizing hybridomas.

The method reported here describes a microrosetting assay which allows the early detection of antibody-synthesizing hybridomas. This method is specific, requires very few hybridoma cells and avoids artifacts resulting from the presence of antibodies secreted by spleen cells in the primary hybridoma cultures. It is easy to perform and allows the screening of more than one hundred independent clones within a few hours.

Animals↗