Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory.
Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory.
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DOI：
10.1084/jem.20120127
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发表时间：
2012-10-22
期刊：
影响因子：
--
通讯作者：
Takemori T
中科院分区：
文献类型：
--
作者：
Kaji T;Ishige A;Hikida M;Taka J;Hijikata A;Kubo M;Nagashima T;Takahashi Y;Kurosaki T;Okada M;Ohara O;Rajewsky K;Takemori T
B细胞记忆是沿着沿着两条根本不同的细胞分化途径产生的。抗体系统中记忆的一个组成部分是长寿命记忆B细胞，其被选择用于在T细胞依赖性生发中心（GC）反应中表达体细胞突变的高亲和力抗体。一个令人困惑的观察是，记忆B细胞区室也包含表达未突变的低亲和力抗体的细胞。使用有条件的Bcl 6消融，我们证明，这些细胞是通过增殖扩增免疫后早期产生的T细胞依赖性，但GC独立的方式。它们很快变得静止和长寿，并显示出一种新的独特的基因表达特征，该特征将记忆B细胞与其他类别的B细胞区分开来。GC非依赖性记忆B细胞随后与体细胞突变的GC后代以大致相等的比例连接，并且这两种类型的记忆细胞有效地产生过继性二次抗体应答。T滤泡辅助细胞（Tfh）的缺失显著减少了应答早期突变记忆细胞的产生，但未突变记忆细胞的产生并没有减少。因此，B细胞记忆是沿着沿着两条根本不同的细胞分化途径产生的。一种途径致力于产生高亲和力的体细胞抗体突变体，而另一种保留生殖系抗体特异性，并可能使生物体对入侵病原体的抗原变体做出快速反应。
B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One component of memory in the antibody system is long-lived memory B cells selected for the expression of somatically mutated, high-affinity antibodies in the T cell–dependent germinal center (GC) reaction. A puzzling observation has been that the memory B cell compartment also contains cells expressing unmutated, low-affinity antibodies. Using conditional Bcl6 ablation, we demonstrate that these cells are generated through proliferative expansion early after immunization in a T cell–dependent but GC-independent manner. They soon become resting and long-lived and display a novel distinct gene expression signature which distinguishes memory B cells from other classes of B cells. GC-independent memory B cells are later joined by somatically mutated GC descendants at roughly equal proportions and these two types of memory cells efficiently generate adoptive secondary antibody responses. Deletion of T follicular helper (Tfh) cells significantly reduces the generation of mutated, but not unmutated, memory cells early on in the response. Thus, B cell memory is generated along two fundamentally distinct cellular differentiation pathways. One pathway is dedicated to the generation of high-affinity somatic antibody mutants, whereas the other preserves germ line antibody specificities and may prepare the organism for rapid responses to antigenic variants of the invading pathogen.
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