The molecular evolution of the immune response: idiotope-specific suppression indicates that B cells express germ-line-encoded V genes prior to antigenic stimulation.
Antibodies expressed by the immune B cell population are characterized by variable region amino acid substitutions resulting from somatic nucleotide replacement (somatic mutation). This is not true of antibodies expressed by the "naive" B cell population. It is at present unclear whether this discrepancy is due to the preferential clonal selection of a pre-existing subpopulation of naive B cells that express variable regions altered via nucleotide replacement, or whether the process of nucleotide replacement occurs only during the antigen-dependent stages of B cell differentiation. To address this question we have used anti-idiotypic suppression to functionally delete B cells that express particular variable-region structures from the antigen-responsive repertoire. Suppression of the major cross-reactive idiotype (IdCR) expressed in strain A mice in response to p-azophenylarsonate (Ars) was induced using the monoclonal anti-IdCR antibody AD8. The idiotope recognized by AD8 is easily destroyed by alteration of IdCR variable-region structure via nucleotide replacement. The IdCR anti-Ars immune repertoire is characterized by antibodies that lack the AD8-cognate idiotope due to nucleotide replacement. However, complete suppression of the IdCR could reproducibly be achieved by administration of AD8 prior to Ars immunization. This result indicates that all IdCR-expressing B cells also express the AD8-cognate idiotope prior to immunization. Thus, somatic nucleotide replacement must occur exclusively during the antigen-dependent stages of B cell differentiation in this system.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000916:Antibody Diversity; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D007108:Immune Tolerance; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008805:Mice, Inbred A / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region