MATURATION OF THE IMMUNE-RESPONSE IN GERMINAL-CENTERS
MATURATION OF THE IMMUNE-RESPONSE IN GERMINAL-CENTERS
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DOI：
10.1016/0092-8674(91)90289-b
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发表时间：
1991-12-20
期刊：
影响因子：
64.5
通讯作者：
APEL, M
中科院分区：
文献类型：
--
作者：
BEREK, C;BERGER, A;APEL, M
在初次免疫应答期间，生发中心在外周淋巴组织中形成，并且可能在亲和力成熟过程中起关键作用。我们比较了在小鼠对2 - 苯 - 噁唑酮（phOx）的免疫应答过程中，生发中心内和生发中心外的B细胞的抗原特异性库的多样化。通过对phOx特异性抗体所特有的V（κ）Ox1轻链进行测序，我们表明体细胞突变在生发中心B细胞中积累，并且赋予高亲和力结合的突变出现频率增加。对V/D/J重排的分析表明，这种突变在许多B细胞中独立发生，然后这些B细胞优先扩增。我们得出结论，尽管超突变机制可能在生发中心形成之前就被激活，但通过超突变和选择实现的亲和力成熟发生在生发中心。
Germinal centers develop in peripheral lymphatic tissue during the primary immune response and may play a crucial role in affinity maturation. We have compared the diversification of the antigen-specific repertoire of B cells, both from within and from outside the germinal centers, during the murine response to 2-phenyl-oxazolone (phOx). By sequencing V(kappa)Ox1 L-chains characteristic of phOx-specific antibodies, we show that somatic mutations accumulate in germinal center B cells and that a mutation conferring high affinity binding is found with increasing frequency. An analysis of V/D/J rearrangements suggests that this mutation occurred independently in many B cells, which were then preferentially expanded. We conclude that, although the hypermutation mechanism may be activated before germinal centers develop, affinity maturation by hypermutation and selection takes place in the germinal centers.