Affinity dependence of the B cell response to antigen: A threshold, a ceiling, and the importance of off-rate
Affinity dependence of the B cell response to antigen: A threshold, a ceiling, and the importance of off-rate
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DOI：
10.1016/s1074-7613(00)80580-4
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发表时间：
1998-06-01
期刊：
影响因子：
32.4
通讯作者：
Neuberger, MS
中科院分区：
文献类型：
--
作者：
Batista, FD;Neuberger, MS
体液免疫应答的启动和亲和力成熟由抗原与BCR的相互作用驱动。为了研究通过BCR的信号传导和抗原呈递如何依赖于抗原/BCR亲和力，用结合动力学不同的突变溶菌酶攻击溶菌酶特异性B细胞转染子。对于可检测的触发，抗原/BCR复合物需要K-a > 10（6）M-1（解离半衰期>类似于1 s）。然而，如果与可溶性抗体复合，则可以呈现结合力低于该阈值的突变溶菌酶。在阈值以上，触发应答所需的抗原浓度随着亲和力（特别是解离半衰期）增加而降低。然而，在K（a）s >类似于10（10）M-1（解离半衰期> 0.5小时）时达到平台，支持亲和力成熟的上限的想法。
Initiation and affinity maturation of the humoral immune response is driven by antigen interaction with BCR. To study how signaling and antigen presentation through BCR depend on antigen/BCR affinity, lysozyme-specific B cell transfectants were challenged with mutated lysozymes differing in their binding kinetics. For detectable triggering, the antigen/BCR complex needed a K-a > 10(6) M-1 (dissociation half-life > similar to 1 s). Mutated lysozymes whose binding was below this threshold could nevertheless be presented if complexed with soluble antibody. Above the threshold, the concentration of antigen required to trigger a response decreased as the affinity (particularly dissociation half-life) increased. However, a plateau was reached at K(a)s > similar to 10(10) M-1 (dissociation half-life > 0.5 hr), supporting the idea of a ceiling to affinity maturation.