Berek C, Berger A, Apel M
Institut für Genetik, Köln, Germany.
Cell. 1991 Dec 20;67(6):1121-9. doi: 10.1016/0092-8674(91)90289-b.
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-phenyloxazolone (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.
生发中心在初次免疫反应期间于外周淋巴组织中形成，并且可能在亲和力成熟过程中发挥关键作用。我们比较了在小鼠对2-苯基恶唑酮（phOx）的反应过程中，生发中心内外B细胞抗原特异性库的多样化情况。通过对phOx特异性抗体特征性的VκOx1轻链进行测序，我们发现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不断增加。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，随后这些B细胞被优先扩增。我们得出结论，尽管高突变机制可能在生发中心形成之前就被激活，但通过高突变和选择实现的亲和力成熟发生在生发中心。
