High affinity IgM+ memory B cells are generated through a germinal center-dependent pathway

High affinity IgM+ memory B cells are generated through a germinal center-dependent pathway
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DOI:
10.1016/j.molimm.2015.10.003
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发表时间:
2015-01-01
影响因子:
3.6
通讯作者:
Azuma, Takachika
Azuma, Takachika
中科院分区:
医学3区
文献类型:
--
作者:
Hara, Yasushi;Tashiro, Yasuyuki;Azuma, Takachika

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在 T 细胞依赖性免疫反应过程中,B 细胞经历克隆扩增和选择,并诱导同种型转换和体细胞超突变 (SHM)。尽管体细胞突变的IgM(+)记忆B细胞已有报道,但尚未确定它们是否真的是高亲和力B细胞。我们根据 B 细胞受体 (BCR) 的亲和力追踪正常免疫小鼠的 (4-羟基-3-硝基苯基) 乙酰半抗原特异性 GC B 细胞,并进行 BCR 序列分析。 SHM在免疫后第7天就很明显,并随着时间的推移而增加,因此高亲和力IgM(+)以及IgG(+)记忆B细胞持续生成直至第42天。相反,类别转换重组(CSR)在第7天几乎完成,然后IgG1(+)/IgM(+)GC B细胞的比率保持不变。这些发现共同表明,IgM(+) B 细胞在 GC 中经历 SHM,生成高亲和力 IgM+ 记忆细胞,并且即使在 CSR 完成后,该过程仍在继续。 (C) 2015 Elsevier Ltd. 保留所有权利。
During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM+ memory cells and that this process continues even after CSR is accomplished. (C) 2015 Elsevier Ltd. All rights reserved.