B-CD8⁺ T Cell Interactions in the Anti-Idiotypic Response against a Self-Antibody

Figure 8

Model of peripheral tolerance to self-antigens mediated by anti-idiotypic responses involving P3 mAb. Different causes, like chronic infections, cross-reactivity between self and pathogen antigens, or dysfunction of regulatory circuits, can produce the proliferation and activation of B cell-secreting anti-self antibodies, similar to P3 mAb (P3-Id⁺) (1). Some of these antibodies (P3-Id⁺) carry a regulatory idiotope able to bind anti-idiotypic B cells, B-1a αP3-Id, and B-2 αP3-Id (2). These in vivo activated B-1a cells present idiopeptides and secrete cytokines that activate CD4⁺ (Th) and cytotoxic CD8⁺ T cells (CTL) (3). These activated cytotoxic CD8⁺ T cells can kill the anti-self B cells that present the regulatory peptide on their MHC class I, while the activated B cells, most likely B-2, will secrete anti-idiotypic IgG able to block the anti-self antibodies (4).