Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection
Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection
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DOI：
10.1038/ncomms11826
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发表时间：
2016-06-01
影响因子：
16.6
通讯作者：
Jacob, Joshy
中科院分区：
文献类型：
--
作者：
Bohannon, Caitlin;Powers, Ryan;Jacob, Joshy
作为终生保护性抗体的来源，长寿命的浆细胞对体液免疫至关重要。抗原激活的B细胞在T细胞的帮助下，在生发中心内经历亲和力成熟，并在骨髓中作为长期存活的IgG浆细胞存在。在这里，我们展示了抗原特异性的、诱导的IgM浆细胞也可以终生存在。与长期存活的免疫球蛋白浆细胞不同，免疫球蛋白M浆细胞主要保留在脾内，即使在没有生发中心的情况下也可以发育。有趣的是，它们表达的免疫球蛋白基因座显示出由激活诱导的胞苷脱氨酶(AID)引起的体细胞突变。然而，这些IgM浆细胞可能不是抗原选择的，因为替换突变通过可变片段传播，而不是在CDR中浓缩。最后，来自长寿的IgM浆细胞的抗体提供了针对致命病毒挑战的保护性宿主免疫。
Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells-with T-cell help-undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.