Two waves of memory B-cell generation in the primary immune response
Two waves of memory B-cell generation in the primary immune response
复制标题
DOI：
10.1093/intimm/dxh241
复制
发表时间：
2005-05-01
影响因子：
4.4
通讯作者：
Abe, R
中科院分区：
文献类型：
--
作者：
Inamine, A;Takahashi, Y;Abe, R
在 Bcl-6 缺陷小鼠中，记忆 B 细胞的生成可以独立于生发中心 (GC) 的形成和亲和力成熟，但在正常小鼠中，不依赖 GC 的通路对记忆 B 细胞生成的贡献仍不清楚。为了验证这一点，我们在初次反应中GC形成开始时给小鼠注射了抗诱导共刺激剂（ICOS）单克隆抗体。这种操作影响了脾脏中 GC B 细胞的生成，但 IgG1 记忆 B 细胞和 IgG1 长期抗体的生成均不受影响。在 ICOS 操作的小鼠中，GC B 细胞在 IgV(H) 基因中积累体细胞突变并经历亲和力成熟；然而，记忆 B 细胞几乎不积累突变，并通过低亲和力重建次级反应，支持低亲和力记忆 B 细胞以不依赖 GC 的方式产生的观点。因此，记忆 B 细胞似乎是通过两种不同的途径建立的，与或不与 GC 反应和亲和力成熟相关。 ICOS 操作小鼠中低亲和力 IgG1 记忆 B 细胞和抗体的产生和长期持续支持了低亲和力记忆 B 细胞可能产生长期抗体形成细胞的观点。
Memory B cells can be generated independently of germinal center (GC) formation and affinity maturation in Bcl-6-deficient mice, but the contribution of the GC-independent pathway for memory B-cell generation in normal mice remains unknown. To examine this, we administrated anti-inducible co-stimulator (ICOS) mAbs into mice at the onset of GC formation in the primary response. This manipulation affected the generation of GC B cells in the spleen, but neither IgG1 memory B cell nor production of IgG1 long-term antibody was affected. In ICOS-manipulated mice, GC B cells accumulated somatic mutations in the IgV(H) genes and underwent affinity maturation; however, memory B cells scarcely accumulated mutations and reconstituted the secondary response by low affinity, supporting the notion that low-affinity memory B cells are generated in a GC-independent manner. Thus, it appears that memory B cells are established by two different pathways, associated with or without GC reaction and affinity maturation. The generation and long-term persistence of low-affinity IgG1 memory B cells and antibodies in ICOS-manipulated mice support the idea that low-affinity memory B cells may give rise to long-term antibody-forming cells.