T-cell dependent response to immune complexes abrogates B-cell unresponsiveness to pneumococcal cell wall polysaccharide

Abstract

Although > 90% of B cells from M167 (mu, kappa) immunoglobulin transgenic (Tg) mice express surface immunoglobulin that binds phosphorylcholine (PC), we found that these mice are unresponsive to immunization with pneumococcal cell wall polysaccharide (PnC), a type II thymus-independent antigen that contains PC. However, when the PnC antigen was presented as a complex with TEPC-15 or McPC-603 antibodies (which are specific for PnC), a vigorous immune response occurred in which the Tg mice produced 10-50-fold more anti-PnC antibody than when immunized with antigen alone. Interestingly, MOPC-167, which expresses the VH and VL regions used to encode the transgene antibody, was found to be a relatively poor 'carrier' for PnC, eliciting a weak anti-PnC antibody response 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 to 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 transgene-encoded idiotype.