Structured reactions of serum IgM repertoires to immunization are dependent on major histocompatibility complex genes

In normal animals, responses to immunization include alterations in the ser um ISM antibody repertoire, as scored on autologous tissue antigens with no respect for the immunizing antigen. These immunogen-nonspecific antibody r eactions 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 un der the control of MHC-Linked genes, including a class I locus. This strong ly suggests the involvement of T cells restricted by both class I and class II MHC, in regulating serum IgM repertoires. Immunogen-nonspecific reperto ire reactions to immunization may, therefore, represent degenerate, but pro totypical, reactions or regulatory mechanisms embodying the natural reperto ires of T- and B cells connected to autoantigens. Natural (auto)immunity co uld so serve to regulate the effector class of adaptive immune responses, p articularly in order to avoid pathogenic autoreactivity following specific immunization with self-cross-reacting antigens. Appropriate analysis of non specific repertoire reactions could therefore contribute to the understandi ng of general structures of immune regulation and natural tolerance.