KINETIC MATURATION OF AN IMMUNE-RESPONSE

KINETIC MATURATION OF AN IMMUNE-RESPONSE
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DOI:
10.1038/352530a0
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发表时间:
1991-08-08
期刊:
影响因子:
64.8
通讯作者:
MILSTEIN, C
MILSTEIN, C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
FOOTE, J;MILSTEIN, C

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抗体的亲和力成熟是受热力学还是动力学控制,还是两者兼而有之?我们比较了来自2-苯基-5-恶唑酮特异性杂交瘤的抗体从一次、二次和三次反应中与半抗原结合的物理常数。除了平衡常数的增加外,在对具有极高开启速率常数的免疫球蛋白家族进行初步反应后,抗体谱系也发生了变化。尽管这组抗体的亲和力一般或低于平均水平,但这种转变还是发生了。这与B淋巴细胞增殖受到动力学选择的影响是一致的,优先于快速结合靶抗原,同时也是基于紧密结合的热力学选择。
IS the affinity maturation of antibodies under thermodynamic or kinetic control, or both? We compared the physical constants of hapten binding by antibodies from 2-phenyl-5-oxazolone-specific hybridomas from primary, secondary and tertiary responses. In addition to an increase in equilibrium constant, there was a shift in the antibody repertoire after the primary response towards an immunoglobulin family with an extremely high on-rate constant. This shift occurred in spite of the average or below-average affinity of this group of antibodies. This is consistent with B-lymphocyte proliferation being subject to a kinetic selection, with a premium on binding target antigens rapidly, in parallel with a thermodynamic selection based on binding tightly.