T-CELL-DEPENDENT RESPONSE TO IMMUNE-COMPLEXES ABROGATES B-CELL UNRESPONSIVENESS TO PNEUMOCOCCAL CELL-WALL POLYSACCHARIDE

Although > 90% of B cells from M167 (mu, kappa) immunoglobulin transge nic (Tg) mice express surface immunoglobulin that binds phosphorylchol ine (PC), we found that these mice are unresponsive to immunization wi th pneumococcal cell wall polysaccharide (PnC), a type II thymus-indep endent antigen that contains PC. However, when the PnC antigen was pre sented as a complex with TEPC-15 or McPC-603 antibodies (which are spe cific for PnC), a vigorous immune response occurred in which the Tg mi ce produced 10-50-fold more anti-PnC antibody than when immunized with antigen alone. Interestingly, MOPC-167, which expresses the V-H and V -L regions used to encode the transgene antibody, was found to be a re latively poor 'carrier' for PnC, eliciting a weak anti-PnC antibody re sponse in M167 (mu, kappa) Tg mice. In vivo administration of anti-CD4 antibody dramatically reduced the response to TEPC-15/PnC complexes, suggesting that the response is mediated by immunoglobulin (idiotype)- dependent helper T cells. The results indicate that unresponsiveness t o PnC is due not to tolerance of the transgenic B cells but rather to the lack of T-cell help resulting from T-cell tolerance to the transge ne-encoded idiotype.