Identification and characterization of an apparent germline set of auto-anti-idiotypic regulatory B lymphocytes.
By fusing BALB/c splenic lymphocytes from mice immunized with phosphorylcholine (PC) to an immunoglobulin nonproducing plasmacytoma cell line, a B cell hybridoma was isolated (MM-60) that has been shown by multiple criteria to produce a bona fide auto-anti-(anti-T15 idiotype) antibody. In vivo administration of MM-60 antibody suppressed T15+ anti-PC antibody production in an idiotope-specific manner by activation of an intervening set of anti-T15 B cells. These T15-specific B cells i) appeared to express germline-encoded variable region gene products, ii) developed in parallel to, but independent of, T15+ B cells, and iii) suppressed the anti-PC response in a T cell-independent fashion. Variants of T15+ anti-PC B cells possessing aberrant immunoglobulin heavy chain D region structure escaped from the suppression imposed by this anti-T15 B cell set, suggesting that a function of the heavy chain D region may be to contribute to the formation of molecular target sites for idiotype-directed regulatory cells and/or antibodies. The indigenous nature of these particular populations of anti-idiotypic and anti-(anti-idiotypic) B cells and the ability of their immunoglobulin products to regulate antigen-specific B cells in vivo provides strong supportive evidence for the significant role idiotype-directed network interactions play in regulating specific antibody production during a normal immune response.
D000375:Aging; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000032:analysis / Q000302:isolation & purification*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis / Q000302:isolation & purification; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000166:cytology / Q000276:immunology; D001323:Autoantibodies / Q000008:administration & dosage / Q000032:analysis / Q000302:isolation & purification*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D007111:Immunity, Cellular; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology*; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010641:Phenotype
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D007130:Immunoglobulin Idiotypes