IDIOTYPIC REGULATION OF B-CELL DIFFERENTIATION

We study the equilibrium properties of idiotypically interacting B cel l clones in the case where only the differentiation of B cells is affe cted by idiotypic interactions. Furthermore, we assume that clones may recognize and be stimulated by self antigen in the same fashion as by anti-antibodies. For idiotypically interacting pairs of non-autoreact ive clones we observe three qualitatively different dynamical regimes. In the first regime, at small antibody production an antibody-free fi xed point, the virgin state, is the only attractor of the system. For intermediate antibody production, a symmetric activated state replaces the virgin state as the only attractor of the system. For large antib ody production, finally, the symmetric activated state gives way to tw o asymmetric activated states where one clone suppresses the other clo ne. If one or both clones in the pair are autoreactive there is no vir gin state. However, we still observe the switch from an almost symmetr ic activated state to two asymmetric activated states. The two asymmet ric activated states at high antibody production have profoundly diffe rent implications for a self antigen which is recognized by one of the clones of the pair. In the attractor characterized by high autoantibo dy concentration the self antigen is attacked vigorously by the immune system while in the opposite steady state the tiny amount of autoanti body hardly affects the self antigen. Accordingly, we call the first s tate the autoimmune state and the second the tolerant state. In the to lerant state the autoreactive clone is down-regulated by its anti-idio type providing an efficient mechanism to prevent an autoimmune reactio n. However, the antibody production required to achieve this anti-idio typic control of autoantibodies is rather large.