Inverse correlation between the utilization of an idiotype in specific immune responses and its representation in pre-immune "natural" antibodies.
Previously we have characterized an idiotype (Id) that accounts for half of all specific anti-dextran B512 (Dex) antibodies in C57BL/6 mice. BALB/c mice produce the same Id in normal, pre-immune sera but fail to use it in antibody responses to Dex, although Id+ anti-Dex antibodies can be induced in this strain by anti-Id immunization. By limiting dilution analysis of B cell clonal precursors, we show here that the frequencies of Id+ B cells are comparable in both strains, but their state of activity is sharply distinct: while all Id+ B cells are small, resting lymphocytes in C57BL/6 mice, they are all large, naturally activated cells in BALB/c mice. The suggestion that naturally activated cells are poorly engaged in specific responses was supported by the delayed and lower Id+ responses obtained in BALB/c mice when they are immunized, in parallel with C57BL/6 animals, with a conjugate of anti-Id antibodies and lipopolysaccharide. Finally, C57BL/6 responder mice were found to closely reproduce the normal BALB/c situation, if analyzed 3 months after anti-Id priming: they produce low levels of serum Id and all Id+ B cells are in the large lymphocyte compartment. Upon immunization these animals develop serum Id+ responses that are undistinguishable from low-responder BALB/c mice. The relevance of these observations for the questions of physiologic self-reactivity is discussed.
D000818:Animals; D000917:Antibody Formation; D001327:Autoimmune Diseases / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002999:Clone Cells; D003911:Dextrans / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007156:Immunologic Memory; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors
D003911:Dextrans; D007130:Immunoglobulin Idiotypes; D008070:Lipopolysaccharides