Idiotype regulation of self responses, autoantibody V regions and neonatal B cell repertoire

The role of autoantibodies themselves in immune regulation is still unknown. There is evidence that some autoantibody idiotypes (Id) may play a regulatory role in physiologic and possibly pathologic situations of the immune system. Here we present evidence that (1) certain autoantibody Id modulate the immune response to self antigens (regulatory Id), and (2) that the neonatal preimmune repertoire is primarily devoted to self recognition. The humoral and cellular events following immunization with regulatory Id suggest an active participation of T cells in the regulatory events. Based on immunochemical, structural and molecular genetics analysis, it appears that this regulatory Id is of germline origin as it exists within the neonatal preimmune repertoire. B cell hybridomas generated from unstimulated splenocytes of neonatal mice are primarily self-reactive, suggesting that the immune system essentially begins as a self-recognizing system. The findings are discussed with regard to the relationship between germline repertoire, autoantibodies, and regulatory idiotypes.