Selective activation by thymus-dependent antigens of distinct B cell subpopulations expressing a major cross-reactive idiotype.

We determined the B cell subpopulations that produce the major cross-reactive idiotype (CRIA) associated with the anti-phenylarsonate (ARS) antibody response of A/J mice. Specifically, we examined the B2 subpopulation found in normal mice which, in H-2b mice, bears the I-Ab-encoded determinant Ia.W39; the B1 subpopulation found in mice expressing the CBA/N X-linked immunodeficiency trait (xid); and the B1 subpopulation found in normal mice after the cytotoxic elimination of B2 cells with anti-Ia. W39 and complement. CRIA is expressed in each of these B cell subpopulations. Antigen plays a selective role in the stimulation of distinct B cell sets. ARS conjugates of keyhole limpet hemocyanin (KLH) can activate both the B1 and B2 subpopulations. In contrast, ARS conjugates of synthetic polypeptides under Ir gene control selectively activate the B2 subpopulation in strains that are genetic responders to the carrier. This leads to the establishment of CRIA dominance where CRIA+ anti-ARS antibody is 70 to 95% of the total anti-arsonate antibody response. This class of antigens fails to activate the B1 cells in either normal or xid mice. We compared the CRIA+ antibody produced by selectively activated B2 cells to that produced by the B1 subpopulation in xid mice. For these comparisons, we used competitive radioimmunoassays that employed polyspecific anti-CRIA antiserum or monoclonal anti-CRIA antibodies specific for distinct idiotopes on the heavy chain of CRIA+ antibody. B2 cells produce a CRIA+ anti-ARS antibody that is idiotopically uniform among individual mice, and that closely approximates the hybridoma protein 36-65 (the heavy chain of 36-65 represents the germ line-encoded sequence of the unique CRIA structural gene (25]. In contrast, the CRIA+ antibody produced by the B1 cell subset of xid mice is idiotopically diverse among individual mice, and differs markedly from the 36-65 hybridoma protein. The extent of diversification found in CRIA+ antibody depends on the B cell subpopulation that produces it.