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Structured reactions of serum IgM repertoires to immunization are dependent on major histocompatibility complex genes
1Unité d'Immunobiologie, CNRS URA 1961, Institut Pasteur, Paris, France.
In normal animals, responses to immunization include alterations in the serum IgM antibody repertoire, as scored on autologous tissue antigens with no respect for the immunizing antigen. These immunogen-nonspecific antibody reactions were found previously to display specific structures dependent on strain and immunization protocols. Using major histocompatability complex (MHC)-congenic Lewis rats, we show that such IgM repertoire reactions are under the control of MHC-linked genes, including a class I locus. This strongly suggests the involvement of T cells restricted by both class I and class II MHC, in regulating serum IgM repertoires. Immunogen-nonspecific repertoire reactions to immunization may, therefore, represent degenerate, but prototypical, reactions or regulatory mechanisms embodying the natural repertoires of T- and B cells connected to autoantigens. Natural (auto)immunity could so serve to regulate the effector class of adaptive immune responses, particularly in order to avoid pathogenic autoreactivity following specific immunization with self-cross-reacting antigens. Appropriate analysis of nonspecific repertoire reactions could therefore contribute to the understanding of general structures of immune regulation and natural tolerance.
In normal animals, responses to immunization include alterations in the serum IgM antibody repertoire, as scored on autologous tissue antigens with no respect for the immunizing antigen. These immunogen-nonspecific antibody reactions were found previously to display specific structures dependent on strain and immunization protocols. Using major histocompatability complex (MHC)-congenic Lewis rats, we show that such IgM repertoire reactions are under the control of MHC-linked genes, including a class I locus. This strongly suggests the involvement of T cells restricted by both class I and class II MHC, in regulating serum IgM repertoires. Immunogen-nonspecific repertoire reactions to immunization may, therefore, represent degenerate, but prototypical, reactions or regulatory mechanisms embodying the natural repertoires of T- and B cells connected to autoantigens. Natural (auto)immunity could so serve to regulate the effector class of adaptive immune responses, particularly in order to avoid pathogenic autoreactivity following specific immunization with self-cross-reacting antigens. Appropriate analysis of nonspecific repertoire reactions could therefore contribute to the understanding of general structures of immune regulation and natural tolerance.