Contribution of light chain rearrangement in peripheral B cells to the generation of high‐affinity antibodies
Contribution of light chain rearrangement in peripheral B cells to the generation of high‐affinity antibodies
复制标题
外周 B 细胞中轻链重排对高亲和力抗体生成的贡献
DOI：
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发表时间：
2002
影响因子：
5.4
通讯作者：
H. Ohmori
中科院分区：
文献类型：
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作者：
M. Magari;T. Sawatari;Y. Kawano;M. Cascalho;M. Wabl;N. Kanayama;M. Hikida;H. Ohmori
最近，外周B细胞显示免疫球蛋白基因发生继发性V(D)J重排，但这一事件的生理作用尚未完全阐明。为了研究外周L链基因重排是否参与了高亲和力抗体（Ab）的产生，我们使用了17.2.25重排VHDJH基因（VHT）敲入小鼠，其B细胞多样性由于位点定向转基因的表达而受到限制。用对硝基苯乙酰（pNP）偶联鸡γ -球蛋白免疫小鼠可优先产生由非VHT编码的H链和λ链组成的抗pNP IgG Ab。λ+ IgG构成了大部分对该半抗原具有高亲和力的Ab。在免疫小鼠的引流淋巴结中，RAG‐2 mRNA和λ1基因重组信号序列断裂增加，而在未免疫小鼠中则没有增加。这些与λ基因重排相关的参数水平与λ+高亲和力抗pNP IgG的产生密切相关。这些观察结果在用敲入小鼠的脾脏细胞重组的RAG‐1‐缺陷小鼠中重现。因此，我们的研究结果表明，发生在外周的L链重排可能有助于Ab的亲和成熟。
Recently, peripheral B cells have been shown to undergo secondary V(D)J rearrangement of immunoglobulin genes, but the physiological role of this event has not been fully elucidated. To investigate whether rearrangement of L chain genes in the periphery is involved in the generation of high‐affinity antibodies (Ab), we used the 17.2.25 rearranged VHDJH gene (VHT)‐knockin mouse whose B cell diversity is limited due to the expression of the site‐directed transgene. Immunization of the mouse with p‐nitrophenylacetyl (pNP)‐conjugated chicken γ‐globulin preferentially led to the production of anti‐pNP IgG Ab comprised of non‐VHT‐encoded H chains and λ chains. λ+ IgG constituted a majority of high‐affinity Ab to this hapten. RAG‐2 mRNA and the recombination signal sequence break of the λ1 gene increased in the draining lymph node of immunized mice, but not of nonimmunized animals. There was a close correlation between the levels of these parameters implicating λ gene rearrangement and the production of λ+ high‐affinity anti‐pNP IgG. These observations were reproduced in RAG‐1‐deficient mice that were reconstituted with the spleen cells ofthe knockin mouse. Thus, our findings suggest that L chain rearrangement that occurs in the periphery can contribute to affinity maturation of Ab.
影响因子：
56.9
作者：
Papavasiliou, F;Casellas, R;Nussenzweig, MC
通讯作者：
Nussenzweig, MC