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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells.
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Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells.

机译：人类浆细胞系统成熟过程中IGHV基因体细胞超突变的调节选择。

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摘要

Systemic antigen-induced PCs are generated in inductive lymphoid tissues. Some of them are selected to travel through the circulation and finally, to home onto BM niches. BM PCs show prolonged survival and secrete high-affinity antibodies. In this study, human PCs were isolated from tonsil, blood, and BM, their IGHV3 and IGHV6 genes were sequenced, and their SHM were evaluated. The SHM analysis reveals the existence of a maturational gradient in these genes, as demonstrated by a progressive increase in the frequency of total and R mutations and total and NC aa changes following the direction: tonsil --> blood --> BM. The ratio of R to S mutations in the CDR1 and -2, but not in the FRs, increases from tonsil to blood and BM; this parameter reaches a maximum threshold when more than 10 mutations/sequence occur. Further analyses indicate that CDR1 and CDR2 SHM followed different strategies to provide appropriate amino acid changes, but both exhibited maximal resistance to incorporating drastic molecular alterations in the BM PCs. Finally, all of the findings are similar in IGHV3 and IGHV6 sequences, indicating that they reflect general rules imposed by in vivo antigen selection.
机译：全身性抗原诱导的PC在诱导性淋巴组织中产生。他们中的一些人被选中穿越循环，最后回到BM生态位。 BM PC显示延长的生存期并分泌高亲和力抗体。在这项研究中，从扁桃体，血液和BM中分离出人类PC，对其IGHV3和IGHV6基因进行测序，并评估其SHM。 SHM分析揭示了这些基因中存在成熟梯度，这可以通过总和R突变的频率逐渐增加以及总和NC aa遵循以下方向的变化来证明：扁桃体->血液-> BM。 CDR1和-2中R与S突变的比率从扁桃体到血液和BM增加，但在FR中则没有。当发生超过10个突变/序列时，此参数达到最大阈值。进一步的分析表明，CDR1和CDR2 SHM遵循不同的策略来提供适当的氨基酸变化，但在结合BM PC中发生剧烈的分子改变时都表现出最大的抵抗力。最后，所有发现在IGHV3和IGHV6序列中都是相似的，表明它们反映了体内抗原选择所施加的一般规则。

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