Genetic control of natural antibody repertoires: I. IgH, MHC and TCRβ loci

Global analysis of natural antibody repertoires has revealed a marked conservation of reactivity patterns within inbred mouse strains, and characteristic strain‐specific differences. We have now analyzed the genetic control of reactivity repertoires, aiming at identifying the respective selection mechanisms. Multiparametric statistics of a large number of serum antibody reactivities scored by quantitative Western blot analyses using extracts from homologous tissues and bacteria readily distinguish the reactivity patterns of C57BL/6 and BALB/c, revealing homogeneity among genetically identical individuals. Antibody repertoires in the prototype strains can also be segregated from those expressed by the respective IgH congenics, BC.8 and CB.20, demonstrating that IgH‐linked genes contribute to determining natural antibody repertoires. Conversely, strains sharing IgH haplotype also express distinct reactivity patterns, indicating that other genes participate in the selection of serum IgM repertoires. Two such non‐IgH loci were now identified. Thus, analysis of four MHC‐congenic strains demonstrated that MHC‐linked control of natural antibody repertoires is likely to operate through differential selection of T cell repertoires, since (1) mice that are congenic at the TCRβ locus, and (2) BALB/c nude mice grafted at birth with pure thymic epithelium from either C57BL/6 or BALB/c also differ in their natural antibody repertoires.

[1]  A. Coutinho,et al.  The repertoire of serum IgM in normal mice is largely independent of external antigenic contact , 1997, European journal of immunology.

[2]  A. Coutinho,et al.  A model of the immune network with B-T cell co-operation. I--Prototypical structures and dynamics. , 1996, Journal of theoretical biology.

[3]  A. Coutinho,et al.  A model of the immune network with B-T cell co-operation. II--The simulation of ontogenesis. , 1996, Journal of theoretical biology.

[4]  A. Coutinho,et al.  The Age‐Associated Increase in Autoreactive Immunoglobulins Reflects a Quantitative Increase in Specificities Detectable at Lower Concentrations in Young Mice , 1996, Scandinavian journal of immunology.

[5]  M. Wabl,et al.  A Quasi-Monoclonal Mouse , 1996, Science.

[6]  A. Coutinho,et al.  Evidence for a Thymus‐Dependent Form of Tolerance that is Not Based on Elimination or Anergy of Reactive T cells , 1996, Immunological reviews.

[7]  A. Coutinho,et al.  Analysis of the natural human IgG antibody repertoire: life‐long stability of reactivities towards self antigens contrasts with age‐dependent diversification of reactivities against bacterial antigens , 1995, European journal of immunology.

[8]  A. Coutinho,et al.  Studies on the T cell dependence of natural IgM and IgG antibody repertoires in adult mice , 1995, European journal of immunology.

[9]  A. Coutinho,et al.  Invariance and restriction toward a limited set of self-antigens characterize neonatal IgM antibody repertoires and prevail in autoreactive repertoires of healthy adults. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Coutinho,et al.  Observations on the Mode of Action of Normal Immunoglobulin at High Doses , 1994, Immunological reviews.

[11]  F. Kianifard.  Applied Multivariate Data Analysis: Volume II: Categorical and Multivariate Methods , 1994 .

[12]  A. Coutinho,et al.  Positive and Negative Selection of Antibody Repertoires during B‐Cell Differentiation , 1994, Immunological reviews.

[13]  A. Coutinho,et al.  Global Analysis of Antibody Repertoires. 1. An Immunoblot Method for the Quantitative Screening of a Large Number of Reactivities , 1994, Scandinavian journal of immunology.

[14]  A. Coutinho,et al.  Global analysis of antibody repertoires. II. Evidence for specificity, self‐selection and the immunological “homunculus” of antibodies in normal serum , 1993, European journal of immunology.

[15]  A. Coutinho,et al.  The Role of Thymic Epithelium in the Establishment of Transplantation Tolerance , 1993, Immunological reviews.

[16]  A. Coutinho,et al.  Transplantation tolerance is unrelated to superantigen-dependent deletion and anergy. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[17]  A. Coutinho,et al.  Differential expression of VH gene families in peripheral B cell repertoires of newborn or adult immunoglobulin H chain congenic mice , 1992, The Journal of experimental medicine.

[18]  I. Cohen,et al.  Autoimmunity, microbial immunity and the immunological homunculus. , 1991, Immunology today.

[19]  T. Ternynck,et al.  IgG autoantibody activity in normal mouse serum is controlled by IgM. , 1990, Journal of immunology.

[20]  A. Coutinho,et al.  Selective peripheral expansion and activation of B cells expressing endogenous immunoglobulin in μ‐transgenic mice , 1990, European journal of immunology.

[21]  A. Coutinho,et al.  Thymic epithelium tolerizes for histocompatibility antigens. , 1990, Science.

[22]  P. Pereira,et al.  Major histocompatibility complex‐linked and t cell‐dependent selection of antibody repertoires. quantitation of i‐e‐related specificities in normal mice* , 1989, European journal of immunology.

[23]  A. Coutinho,et al.  Beyond Clonal Selection and Network , 1989, Immunological reviews.

[24]  P. Pereira,et al.  B cell participation in the recursive selection of T cell repertoires , 1988, European journal of immunology.

[25]  J. Kyhse-Andersen.  Electroblotting of multiple gels: a simple apparatus without buffer tank for rapid transfer of proteins from polyacrylamide to nitrocellulose. , 1984, Journal of biochemical and biophysical methods.

[26]  S. Chensue,et al.  Population dynamics of T and B lymphocytes in the lymphoid organs, circulation, and granulomas of mice infected with Schistosoma mansoni. , 1979, The American journal of tropical medicine and hygiene.

[27]  O. Mäkelä,et al.  Inherited Immunoglobulin Idiotypes of the Mouse , 1977, Immunological reviews.

[28]  A. Coutinho,et al.  Natural autoantibodies. , 1995, Current opinion in immunology.

[29]  A. Coutinho,et al.  Physiopathology of Autoimmunity: The Reactivities of Natural Antibodies Define the Boundaries of the Immunological Self , 1993 .

[30]  S. Avrameas.  Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton'. , 1991, Immunology today.

[31]  P. Pereira,et al.  V-region connectivity in T cell repertoires. , 1989, Annual review of immunology.

[32]  P. Pereira,et al.  Selection of lymphocyte repertoires: the limits of clonal versus network organization. , 1989, Cold Spring Harbor symposia on quantitative biology.

[33]  P. Pereira,et al.  A functional idiotypic network of T helper cells and antibodies, limited to the compartment of “naturally” activated lymphocytes in normal mice , 1987, European journal of immunology.

[34]  A. Coutinho,et al.  Autonomous activation of B and T cells in antigen‐free mice , 1986, European journal of immunology.

[35]  Robbert Benner,et al.  Isotypes and specificities of immunoglobulins produced by germ‐free mice fed chemically defined ultrafiltered “antigen‐free” diet , 1984, European journal of immunology.

[36]  A. Coutinho,et al.  Reactions among IgM antibodies derived from normal, neonatal mice , 1984, European journal of immunology.