Sulzer B, Weisbuch G
Sante Fe Institute, NM 87501, USA.
Bull Math Biol. 1995 Nov;57(6):841-64. doi: 10.1007/BF02458297.
We study the equilibrium properties of idiotypically interacting B cell clones in the case where only the differentiation of B cells is affected 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-autoreactive clones we observe three qualitatively different dynamical regimes. In the first regime, at small antibody production an antibody-free fixed 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 antibody production, finally, the symmetric activated state gives way to two asymmetric activated states where one clone suppresses the other clone. If one or both clones in the pair are autoreactive there is no virgin state. However, we still observe the switch from an almost symmetric activated state to two asymmetric activated states. The two asymmetric activated states at high antibody production have profoundly different implications for a self antigen which is recognized by one of the clones of the pair. In the attractor characterized by high autoantibody concentration the self antigen is attacked vigorously by the immune system while in the opposite steady state the tiny amount of autoantibody hardly affects the self antigen. Accordingly, we call the first state the autoimmune state and the second the tolerant state. In the tolerant state the autoreactive clone is down-regulated by its anti-idiotype providing an efficient mechanism to prevent an autoimmune reaction. However, the antibody production required to achieve this anti-idiotypic control of autoantibodies is rather large.
我们研究了在仅B细胞分化受独特型相互作用影响的情况下，独特型相互作用的B细胞克隆的平衡特性。此外，我们假设克隆可以以与抗抗体相同的方式识别自身抗原并受到其刺激。对于独特型相互作用的非自身反应性克隆对，我们观察到三种定性不同的动力学状态。在第一种状态下，在抗体产生量较小时，无抗体固定点即初始状态是系统的唯一吸引子。在抗体产生量处于中等水平时，一个对称的激活状态取代初始状态成为系统的唯一吸引子。最后，在抗体产生量较大时，对称激活状态让位于两个不对称激活状态，其中一个克隆抑制另一个克隆。如果这对克隆中的一个或两个是自身反应性的，则不存在初始状态。然而，我们仍然观察到从几乎对称的激活状态向两个不对称激活状态的转变。在高抗体产生量时的这两个不对称激活状态对于由这对克隆中的一个克隆识别的自身抗原有截然不同的影响。在以高自身抗体浓度为特征的吸引子状态下，自身抗原会受到免疫系统的强烈攻击，而在相反的稳定状态下，微量的自身抗体几乎不会影响自身抗原。因此，我们将第一种状态称为自身免疫状态，第二种称为耐受状态。在耐受状态下，自身反应性克隆通过其抗独特型而下调，这提供了一种预防自身免疫反应的有效机制。然而，实现对自身抗体的这种抗独特型控制所需的抗体产生量相当大。
