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.