The immune response against anti-idiotope antibodies II. The induction of antibodies bearing the target idiotope (Ab3 beta) depends on the frequency of the corresponding B cells.
In the present study we use two monoclonal anti-idiotope antibodies (Ac38 and Ac146; Ab1) against the germ line-encoded, lambda 1 chain-bearing and (4-hydroxy-3-nitrophenyl)acetyl (NP)-binding antibody B1-8 (Ab1) for the induction of complementary antibodies (Ab3) and ask the question to what extent antibodies bearing B1-8-like idiotopes (Ab3 beta) are represented in the Ab3 population. In this experimental system, Ab3 beta is distinguished from the remaining Ab3 population (Ab3 alpha) by three properties which Ab3 beta may share with B1-8: (a) the binding of NP, (b) the binding to Ac146 (if induced by Ac38) or the binding to Ac38 (if induced by 146) and (c) that they carry lambda 1 chains. Antibodies with all three properties are induced in low amounts by both anti-idiotopes. Also, Ac146 induces only Ab3 alpha (bearing kappa chains and not binding NP and Ac38). In contrast, Ac38 triggers almost exclusively a lambda 1 chain-bearing response, i.e. Ab3 beta. The response has an unusually large size, reaches its maximum after a week and is long-lasting. An analysis at the level of lipopolysaccharide-reactive precursor B cells demonstrates that, in this case, cells expressing Ab3 beta occur at exceedingly high frequency (approximately equal to 10(-3] and are at least 10 times more frequent than cells expressing Ab3 alpha. The high frequency of Ab3 beta-expressing cells correlates with the contribution of several VH, D and J genes to the expression of this particular idiotope. In the case of the Ac146 anti-idiotope antibody, the response is dominated by Ab3 alpha. Ab3 beta represents less than 10% of the total response, reaches maximal levels 2 weeks after immunization and declines rapidly. This correlates with a low frequency of precursor B cells expressing Ab3 beta (approximately equal to 10(-5] and a restriction of the corresponding idiotope to rare VH-D combinations, caused presumably by a stringent contribution of the H chain to this idiotope which covers the NP-binding site. Our data suggest that anti-idiotypic antibodies (Ab2) against Ab1 will preferentially induce antibodies idiotypically related to Ab1 if the corresponding idiotopes are expressed in high frequency in the B cell compartment. This is expected in cases where Ab2 recognizes an idiotope that can be formed by many germ line-encoded VH-D-VL-combinations.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis / Q000276:immunology*; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007145:Immunoglobulin kappa-Chains / Q000032:analysis / Q000276:immunology; D007146:Immunoglobulin lambda-Chains / Q000032:analysis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008070:Lipopolysaccharides