de Boer R J, Hogeweg P
Bioinformatics Group, University of Utrecht, The Netherlands.
J Theor Biol. 1989 Jul 10;139(1):17-38. doi: 10.1016/s0022-5193(89)80055-4.
Previous work was concerned with symmetric immune networks of idiotypic interactions amongst B cell clones. The behaviour of these networks was contrary to expectations. This was caused by an extensive percolation of idiotypic signals. Idiotypic activation was thus expected to affect almost all (greater than 10(7] B cell clones. We here analyse whether the incorporation of helper T cells (Th) into these B cell models could cause a reduction in the percolation. Empirical work on idiotypic interactions between Th and B cells however, would suggest that two different idiotypic Th models should be developed: (1) a Th which recognises native B cell idiotypes, i.e. a non-MHC-restricted "ThId" model, and (2) a "classical" MHC-restricted helper T cell model. In the ThId model, the Th-B cell interaction is symmetric. A 2-D model of a Th and a B cell clone that interact idiotypically with each other accounts for various equilibria (i.e. one virgin and two immune states). Introduction of antigen does indeed lead to a state switch from the virgin to the immune state; such a system is thus able to "remember" its exposure to antigen. Idiotypic signals do however, percolate in ThId models via these "B-Th-B-Th" pathways: proliferating Th and B cell clones that interact idiotypically, will always activate each other reciprocally. In the MHC-restricted Th model, Th-B interactions are asymmetric. Because the B cell idiotypes are processed and subsequently presented by MHC molecules, the Th receptor and the native B cell receptor are not expected to be complementary. Thus the Th and the B cells are unable to activate each other reciprocally, and a 2-D Th-B cell model cannot account for idiotypic memory. In contrast to the ThId model, idiotypic activation cannot percolate via "B-Th-B-Th" interactions. Due to the assymmetry idiotypic activation stops at the first Th level. A Th clone cannot activate a subsequent B cell clone: if the B cells recognise the Th cells, they see idiotype but get no help; if the Th cells see the B cells, the B cells are helped but see no idiotype. The percolation along "B-B-B" pathways in these two models is next analysed. Two B cells clones, each helped by one Th clone, are connected by a symmetric idiotypic interaction. It turns out that in both models the second (i.e. anti-idiotypic) B cells (B2) never proliferate.(ABSTRACT TRUNCATED AT 400 WORDS)
以往的研究关注的是B细胞克隆之间独特型相互作用的对称免疫网络。这些网络的行为与预期相反。这是由独特型信号的广泛渗透导致的。因此，独特型激活预计会影响几乎所有（超过10⁷个）B细胞克隆。我们在此分析将辅助性T细胞（Th）纳入这些B细胞模型是否会导致渗透作用的降低。然而，关于Th细胞与B细胞之间独特型相互作用的实证研究表明，应该建立两种不同的独特型Th细胞模型：（1）一种识别天然B细胞独特型的Th细胞，即非MHC限制性的“ThId”模型，以及（2）一种“经典的”MHC限制性辅助性T细胞模型。在ThId模型中，Th细胞与B细胞的相互作用是对称的。一个Th细胞和一个B细胞克隆相互进行独特型相互作用的二维模型可以解释各种平衡状态（即一种未激活状态和两种免疫状态）。引入抗原确实会导致从未激活状态向免疫状态的转变；这样的系统因此能够“记住”其对抗原的接触。然而，在ThId模型中，独特型信号确实会通过这些“B-Th-B-Th”途径渗透：相互进行独特型相互作用的增殖性Th细胞和B细胞克隆总是会相互激活。在MHC限制性Th细胞模型中，Th细胞与B细胞的相互作用是不对称的。由于B细胞独特型是经过加工后由MHC分子呈递的，预计Th细胞受体与天然B细胞受体不会互补。因此，Th细胞和B细胞无法相互激活，并且二维Th细胞 - B细胞模型无法解释独特型记忆。与ThId模型不同，独特型激活无法通过“B-Th-B-Th”相互作用渗透。由于这种不对称性，独特型激活在第一个Th细胞水平就会停止。一个Th细胞克隆无法激活后续的B细胞克隆：如果B细胞识别Th细胞，它们看到了独特型但得不到帮助；如果Th细胞识别B细胞，B细胞得到了帮助但看不到独特型。接下来分析这两种模型中沿着“B-B-B”途径的渗透情况。两个B细胞克隆，每个都由一个Th细胞克隆辅助，通过对称的独特型相互作用连接。结果发现，在这两种模型中，第二个（即抗独特型）B细胞（B2）都不会增殖。（摘要截取自400字）
