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Biomedical subjects

C Bona

Publications and source records attributed to C Bona.

At least 109 records · Page 6Linked to original sources
PubMed1986

Shared idiotypes and restricted VH genes among murine autoantibodies of various specificities.

The autoantibodies studied here express cross-reactive idiotypes despite the fact that they are heterogeneous with respect to combining site. Furthermore, the presence of cross-reactive idiotypes is independent of the major histocompatibility complex, VH gene usage, and isotype. Similarly, VH gene usage shows that autoantibodies are derived from a restricted number of VH gene families. This restriction is independent of antigen specificity as well as the method of induction (i.e., spontaneous vs. induction). The observation that the VH 7183 gene is predominantly used suggests that certain autoantibodies may be derived from a unique set of B cells such as the Ly1+ B cells. It has been reported that these B cells secrete a high percentage of IgM autoantibodies. The studies reported here may provide greater insight into the genetic and immunoregulatory mechanisms by which autoantibodies arise. The precise mechanisms are not known but may involve both molecular (i.e., VH gene usage) and extracellular (i.e., idiotypic recognition) events.

Animals↗
PubMed1985

Age-dependent isotype variation during secondary immune response in MRL/lpr mice producing autoanti-gamma-globulin antibodies.

A profound inability to produce IgG anti-2,4,6-trinitrophenyl (TNP) antibodies during the secondary immune response elicited by a T-dependent antigen was observed in aged MLR/lpr mice. This unresponsiveness is associated with a significantly low indirect anti-TNP plaque-forming cell response and a weak in vitro anti-TNP response upon the culture of keyhole limpet hemocyanin-primed T cells and TNP-primed B cells in the presence of TNP. The markedly low IgG anti-TNP response observed in aged MLR/lpr mice cannot be related to the presence of rheumatoid factors which are observed during the secondary response, since MRL +/+ and 129/J mice, (non-autoimmune disease strains), also produce significant amounts of anti-gamma-globulin antibodies yet mount a strong IgG anti-TNP response.

Aging↗
PubMed1985

Internal antigen and immune network.

The network hypothesis postulates the existence of internal idiotopic structures which mimic nominal antigens. Experimental evidence for idiotope internal antigen is presented and its implication for the Network hypothesis is discussed. The exploitation of the internal idiotope antigens (or preparation of vaccines) is a realistic possibility.

Animals↗
PubMed1985

Stimulation of human B lymphocytes by Nocardia-delipidated cell mitogen and derived fractions from N. opaca. Structure-activity relationship.

Nocardia-delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, is able to stimulate the proliferation of small resting human B lymphocytes and their differentiation into Ig-secreting cells. This fraction contains two active structures: the cell wall peptidoglycan (PG) and a fraction (Cy I) derived from the cytoplasmic compartment. Treatment of insoluble PG with various bacteriolytic enzymes showed that the minimal structure required for mitogenic activity is more complex than that required for the differentiation of human lymphocytes. The mitogenic activity of cell wall fractions varies in different bacterial species; that prepared from N. opaca is the more potent. Both mitogenic structures of N. opaca induce higher responses in infant and adult PBL as compared to cord lymphocytes. The differentiation of B lymphocytes into Ig-secreting cells induced by PG fractions is T-dependent.

Adjuvants, Immunologic↗
PubMed1984

Expansion of idiotype positive B cells in maternally idiotype suppressed mice.

The membrane expression of the J558 idiotype on B and T lymphocytes was studied in (A/J x BALB/c)F1 and (CAL.20 x BALB/c)F1 mice who were maternally suppressed for this idiotype. Animals suppressed in this fashion exhibit a chronic inability to synthesize J558 Id bearing antibodies in response to an antigenic challenge by alpha 1,3 linked dextran. However, by immunofluorescence, we observed that these maternally suppressed animals actually exhibited a considerable increase of B lymphocytes, which bear endogenously synthesized membrane immunoglobulin expressing the J558-IdI. Furthermore, a subset of T cells emerges that we have previously described as Lyt2.2+ cells exhibiting the J558-IdI determinant, which are capable of transferring the suppression to naïve recipients [1]. The goal of the experiments described in this communication was to thoroughly characterize those B cell clones that are expanded during idiotype suppression. Therefore, we immortalized these J558 Id+ B cells from idiotype suppressed mice as hybridomas. Four hybridomas secreting monoclonal antibodies bearing the J558 IdI but devoid of any specificity for alpha 1,3 linked dextran were obtained. It was established that these monoclonal antibodies bear the J558-Id by two criteria; namely, their direct binding to a panel of monoclonal anti-J558 IdI and a single anti-J558 IdX antibody, as well as by blocking the interaction of J558 with these antibodies. Notable was the fact that they all bore kappa light chains, even though in anti-dextran antibodies the expression of the lambda light chain is required for the expression of this idiotype. These results reaffirm the notion that idiotypic determinants are three dimensional structures which can be reconstructed by a variety of heavy and light chain sequences. Furthermore, an idiotope used in the regulation of an immune response (as our data implicate the J558 IdI is) is borne by antibodies displaying diverse specificities, which are coordinately regulated through this common idiotope.

Animals↗
PubMed1983

Establishment of an inbred line of mice that express a synergistic immune defect precluding in vitro responses to type 1 and type 2 antigens, B cell mitogens, and a number of T cell-derived helper factors.

Introduction of the CBA/N X-linked gene into C3H mice has resulted in the establishment of a new strain of mice that has profound immunologic defects. B cells from these mice show significantly impaired in vitro immune responses to the T cell-independent type 1 antigen trinitrophenyl-Brucella abortus (TNP-BA) as well as markedly reduced proliferative responses to a number of B cell mitogens when compared with the responses of the parental control mice. The in vivo response of such mice to TNP-BA is, however, comparable to that of CBA/N mice. Furthermore, B cells from C3.CBA/N mice are unresponsive to the plaque-forming cell enhancing effects induced by EL4-derived supernatant in the presence of TNP-BA, unlike B cells obtained from CBA/N or C3H/Hen mice whose responsiveness to TNP-BA can be significantly enhanced in the presence of EL4-derived supernatant. The model we have presented to best explain these results suggests that B cells from C3.CBA/N mice can be stimulated only under conditions in which they can interact with carrier-specific T cell help and not under conditions where factor-dependent responses are dominant.

Animals↗
PubMed1983

Idiotypes on B lymphocytes: association with immunoglobulins.

Several idiotypic (Id) specificities have been identified by immunofluorescence on the membranes of B cells in the spleens of nonimmune mice. These determinants are displayed at frequencies varying from 0.22 to 1.83% of B cells and are entirely immunoglobulin (Ig) in nature. No Id determinants were observed on the membranes of four Slg- Abelson virus-transformed pre-B cell lines that are sensitive to LPS. Under our experimental conditions, we did not observe a significant increase in 3H-thymidine incorporation subsequent to the in vitro incubation of splenic lymphocytes from normal mice with various amounts of anti-Id antibodies specific for several cross-reactive (IdX) or individual Id. Similarly, in utero exposure to anti-Id antibodies against myeloma proteins specific for T-independent antigens displaying B cell mitogenic properties did not alter the proliferation of lymphocytes induced by these mitogens. In contrast, exposure to anti-Id antibodies in vitro as well as in utero had a profound and specific effect on the corresponding antibody responses and maturation of small lymphocytes into plasma cells. When normal B cells were cultured with the B cell mitogen LPS in the presence of anti-Id antibodies directed against the J558IdX, specific suppression of the maturation of IdX+ plasma cells was observed. In mice exposed to maternal anti-Id in utero, we observed a severe inability to mount an immune response to any compound that elicited antibody molecules bearing the Id that was complementary to the maternal anti-Id. These same maternally Id-suppressed mice, however, gave a normal response when the same compound was presented as a mitogen. Our results reinforce the concept that Id on membranes of B lymphocytes are associated only with Ig receptors and do not support the possibility of mitogen-like poly-clonal stimulatory properties of anti-Id antibodies.

Animals↗
PubMed1982

Study of the idiotypy of lipopolysaccharide-specific polyclonal and monoclonal antibodies.

The monoclonal antibodies produced by a variety of hybridomas making antibody specific for E. coli 0113 lipopolysaccharide (LPS) were purified by affinity chromatography and their fine specificity studied. All reacted specifically with the polysaccharide moiety of LPS from E. coli 0113 and from Neisseria lactamica; two reacted with LPS from Pseudomonas aeruginosa and one reacted with LPS from Klebsiella pneumoniae. Polyclonal and monoclonal syngeneic and semi-syngeneic anti-idiotypic antisera were produced to study the idiotypy of LPS-specific monoclonal antibodies which express a complex cross-reactive idiotype (IdX) as well as individual idiotypes. E. coli 0113 LPS-specific antibodies produced by BALB/c mice express this IdX and the kinetics for its expression was examined using mice either primed or hyperimmunized with LPS; idiotypic maturation was observed, but we were unable to detect an auto-anti-idiotypic antibody response. This IdX was expressed on E. coli 0113 LPS-specific antibodies from all strains of mice examined, indicating that its expression is not restricted by genes linked to the IgCH locus.

Animals↗
PubMed1981

Neonatal treatment with low doses of anti-idiotypic antibody leads to the expression of a silent clone.

BALB/c mice immunized with bacterial levan (BL) produce an immune response that fails to generate antibody expressing the idiotype (Id) of the beta (2 leads to 6) fructosan-binding myeloma protein ABPC 48 (A48). Pretreatment of newborn BALB/c mice (at 1 d of age) with 0.01-10 microgram of affinity purified BALB/c anti-A48 Id antibody followed by immunization with BL 1-2 mo later produces an anti-BL response that expresses the A48 Id. This shows that A48 Id+ anti-BL clones belong to a normally silent fraction of the anti-BL repertoire. The activation of A48 Id+ anti-BL clones anti-A48 Id antibody is specific because the pretreatment of newborn mice with anti-MOPC 384 Id antibody, followed by immunization with BL, does not lead to its activation. Moreover, pretreatment of mice with anti-A48 Id antibody does not alter the MOPC 460 Id+ component of the anti-TNP response. It is also important to note that the activation of the A48 Id+ clone in pretreated mice requires subsequent immunization with BL.

Animals↗
PubMed1981

Anti-immunoglobulin antibodies. II. Expression of individual and cross-reactive idiotypes on syngeneic and homologous anti-idiotype antibodies.

Syngeneic anti-(anti-Id) antibodies were prepared against BALB/c anti-A48Id antibodies, BALB/c anti-460Id monoclonal antibodies, and A/J anti-J558 IdI monoclonal antibodies. With these anti-(anti-Id) antibodies we identified cross-reactive idiotypes on syngeneic and homologous anti-A48Id and anti-460Id antibodies. By contrast, tbe idiotypic determinants of A/J anti-J558 IdI monoclonal antibodies were not shared by other syngeneic, homologous, or xenogenic anti-J558 IdI or IdX antibodies. These results suggest that idiotype-antiidiotype reactions that serve as regulatory controls within the immune system are characteristic for each particular antigen system, strain, or species and that such interactions make the system self-limited with respect to the whole antild repertoire.

Animals↗
PubMed1980

Anti-immunoglobulin antibodies. I. Expression of cross-reactive idiotypes and Ir gene control of the response to IgG2a of the b allotype.

The anti-allotype antibody response to the b allotypic form of IgG2a is regulated by major histocompatibility complex (MHC)-encoded immune response (Ir) genes. Mice of d, b, p, q, r, and s haplotypes make a strong anti-allotype response on immunization with the CBPC101 myeloma protein (IgG2ab), whereas mice of the k, m, a, a1, u, and z haplotypes made no, or a very poor, response. All responder strains produce anti-IgG2ab antibodies which share common idiotypes (Id) without relation to the allelic forms of the Ig heavy-chain-constant region genes that the responding mice possess. Isoelectric focusing analysis of the anti-allotype antibodies produced in various strains of mice showed that they are of limited heterogeneity and quite similar from strain to strain. Five out of six hybridoma products with specificity for CBPC101 allotype expressed cross-reactive idiotypes (IdX). Two of hybridoma products expressing IdX identify CH3-domain determinants, and one has been assigned a CH2-domain specificity.

Animals↗
PubMed1980

Regulation of the anti-inulin antibody response by a nonallotype-linked gene.

The antibody response to the inulin [(In), beta-(2 leads to 1) fructosan] determinant of bacterial levan [(BL), a beta-(2 leads to 6) polyfructosan that contains beta-(2 leads to 1) branch points] requires the presence of the a haplotype of the Igh gene complex. BALB/c (Igh a) mice immunized with BL produce IgG anti-In antibodies of a single spectrotype by isoelectric focusing analysis. C57BL/6 mice, which possess the b haplotype of the Igh gene complex and which fail to produce anti-In antibodies, nevertheless possess a gene, spectrotype regulation gene 1 (Sr-1), that regulates the isoelectric focusing (IEF) pattern of anti-In antibodies in mice of the a haplotype. Thus, the IEF patterns of anti-In antibodies of (BALB/c x C57BL/6)F1 mice and of B.C8 mice (C57BL/Ka . Igh-Ca) are considerably more complex than those of BALB/c. Backcross analysis indicates that Sr-1 is not linked to the Igh complex, the major histocompatibility complex, or to the genes that code for coat color. Studies of the heterogeneity of anti-In antibodies in recombinant inbred lines and their progeny from matings to BALB/c and C.B20 (BALB/c . Igh-Cb) suggest the existence of other regulatory genes.

Animals↗
PubMed1980

Synergistic genetic defect in B-lymphocyte function. I. Defective responses to B-cell stimulants and their genetic basis.

CBA/N female mice, which express an X-linked defect in B-lymphocyte function, were mated with C3H/HeJ male mice, which are unresponsive to lipopolysaccharide (LPS). The resulting F1 hybrid females were mated to C3H/HeJ males. Approximately one-half of the backcross (BC.1) males obtained from this mating expressed a more profound immunologic defect than either of the parental strains. Spleen cells from these mice were unresponsive to a series of B-cell mitogens including LPS prepared from Escherichia coli K235 and from E. coli 0111:B4, lipoprotein mitogen from E. coli, and Nocardia water-soluble mitogen (NWSM). They failed to give in vitro antibody responses to the thymus-independent type 2 (TI-2) antigen trinophenylated Ficoll and most were unresponsive to the TI-1 antigens trinitrophenylated Brucella abortus, trinitrophenylated LPS, and trinitrophenylated NWSM. This synergistic defect in B-lymphocyte function depended on the presence of the CBA/N xid gene but the critical gene(s) from the C3H strain was not the defective Lps gene (Lpsd). These mice should provide a valuable tool for the elucidation of B-lymphocyte ontogeny, heterogeneity, and function.

Animals↗
PubMed1980

Anti-allotype antibody response in mice: expression of a cross-reactive idiotype and its regulation by auto-anti-idiotypic antibodies in maternally allotype suppressed F1 hybrids.

Anti-IgGb2a allotype antibodies produced by various responder strains of mice expressed a cross-reactive idiotype. This cross-reactive idiotype was evidenced with BAB. 14 and CXBI anti-idiotypic sera raised following immunization with affinity chromatography purified BALB/c anti-CBPC 101 (IgGb2a) antibodies originating from a single BALB/c mouse. F1 hybrids of BALB/c X C.B20 parents, which have been maternally suppressed for IgGb2a allotype as a result of immunization with CBPC 101, produced anti-allotype antibodies lacking cross-reactive idiotype. Furthermore, these mice produced auto-antibodies directed at the IdX of anti-IgGb2a allotypic antibodies.

Animals↗
PubMed1980

Idiotypic network: the MOPC 460 system.

The results presented in this communication show very clearly that the mice with IghCa haplotype can produce anti-TNP antibodies from which a fraction share the idiotypic determinants expressed on M460 myeloma protein. Nevertheless the gene(s) which encode(s) this specificity, is present in the repertoire of strains of mice which have not this haplotype. As in DBA/2 mice this silent clone(s) can be stimulated by an appropriate immunological manipulation and their progeny even can be frozen in hybridomas. The expression of 460 Id positive anti-TNP antibody forming cells is regulated by T cells in BALB/c mice. These T cells are specific for 460 Id and share the idiotypic determinants of anti-460 Id antibodies since they were not found in BALB/c mice with an Ab3 type of response.

Animals↗
PubMed1979

Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes.

The antibody response of BALB/c mice to trinitrophenyl (TNP)-levan or TNP-Nocardia water-soluble mitogen (NWSM) includes a small but significant fraction of antibodies which share idiotypes (Id) with the dinitrophenyl (DNP)- and TNP-binding myeloma protein MOPC-460. Active immunization of BALB/c mice with MOPC-460 or passive administration of anti-460-Id antibodies suppresses the 460-Id+ component of the anti-TNP response. By contrast, active immunization of BALB/c with anti-460-Id antibodies or passive administration of BALB/c anti-[anti-460-Id] antibodies leads to an enhanced 460-Id+ component in the anti-TNP antibodies produced in response to TNP-levan or TNP-NWSM. This enhanced 460-Id+ response appears to be a result of the elimination of suppressor T lymphocytes specific for the 460-Id as T lymphocytes from such mice are unable to suppress the in vitro 460-Id+ response to TNP-NWSM whereas normal T cells are suppressive. These results indicate that suppressor cells specific for 460-Id normally regulate the activation of precursors of cells capable of secreting 460-Id+ anti-TNP antibodies.

Animals↗