Fishman M A, Perelson A S
Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory, NM 87545, USA.
J Theor Biol. 1995 Apr 7;173(3):241-62. doi: 10.1016/s0022-5193(95)80003-4.
The persistence of antigen-specific immune memory appears to require the presence of antigen--suggesting that memory may be due to restimulation of "memory" lymphocytes by persisting antigen. Persistence of antigen, in a form capable of stimulating B cell proliferation, on long-lived, follicular dendritic cells of lymphoid tissue is well documented. Existence of an analogous mechanism for T cell memory maintenance is controversial but can not be ruled out. Here we examine the consequences of immune memory maintenance by antigen-specific lymphocyte restimulation, and estimate the duration of memory as a function of model parameters. We show that the competition for restimulation among memory cell populations results in the selection of the clone having the highest overall affinity for the retained antigen. Thus affinity selection, an important attribute of immunity, is a constitutive property of memory maintenance by antigen-specific restimulation. In the case of B cells, affinity selection is predicted to continue to increase antibody affinity even after somatic mutation stops, and thus may be an important component of affinity maturation. Finally, we discuss several other hypotheses proposed to explain immune memory, including T cell stimulation by cross-reactive antigens.
抗原特异性免疫记忆的持续存在似乎需要抗原的存在——这表明记忆可能是由于持续存在的抗原对“记忆”淋巴细胞的再次刺激所致。抗原以能够刺激B细胞增殖的形式，持续存在于淋巴组织中长寿的滤泡树突状细胞上，这一点已有充分的文献记载。关于T细胞记忆维持的类似机制的存在存在争议，但不能排除。在这里，我们研究了通过抗原特异性淋巴细胞再次刺激来维持免疫记忆的后果，并将记忆持续时间估计为模型参数的函数。我们表明，记忆细胞群体之间再次刺激的竞争导致选择对保留抗原具有最高总体亲和力的克隆。因此，亲和力选择作为免疫的一个重要属性，是通过抗原特异性再次刺激维持记忆的一个固有特性。就B细胞而言，预计即使在体细胞突变停止后，亲和力选择仍会继续增加抗体亲和力，因此可能是亲和力成熟的一个重要组成部分。最后，我们讨论了为解释免疫记忆而提出的其他几种假说，包括交叉反应抗原对T细胞的刺激。
