Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Eur J Immunol. 2013 Aug;43(8):2023-32. doi: 10.1002/eji.201243070. Epub 2013 Jun 12.
In mice, B-1 (B1a/B1b) cells are mainly located in the peritoneal cavity. B-1 cells are well known for their role in the early stages of Ab-mediated immune responses against pathogenic invasion as well as for the production of natural IgM antibodies. Although such B cells have been claimed to give rise to intestinal plasma cells producing IgA, a clear role of B-1 cells in IgA production in the gut-associated tissues is still not defined. Here, we employed the transgenic L2 mouse model characterized by the lack of B-2 cells and presence of B-1 cells as major B-cell subpopulation. The oligoclonality of the Ab repertoire in this mouse allowed us to take typical B1a cell VH sequences as indicators of the presence of IgM-producing B-1a cells in Peyer's patches as well as in lamina propria. However, amongst the IgAVH sequences recovered from the same tissues, none of the sequences showed B1a-cell specificity. Interestingly, all IgAVH sequences derived from the lamina propria of L2 mice displayed extensive numbers of nucleotide exchanges, indicating somatic hypermutation, and affinity maturation. This suggests that the contribution of natural unmutated IgA by B-1a cells to intestinal immunity is negligible.
在小鼠中，B-1（B1a/B1b）细胞主要位于腹腔内。B-1 细胞以其在针对病原体入侵的 Ab 介导的免疫反应的早期阶段的作用以及产生天然 IgM 抗体而闻名。尽管已经声称这些 B 细胞会产生产生 IgA 的肠道浆细胞，但 B-1 细胞在肠道相关组织中产生 IgA 的明确作用仍未确定。在这里，我们使用了缺乏 B-2 细胞且存在 B-1 细胞作为主要 B 细胞亚群的转基因 L2 小鼠模型。该小鼠中 Ab 库的寡克隆性允许我们将典型的 B1a 细胞 VH 序列用作 Peyer 斑以及固有层中存在产生 IgM 的 B-1a 细胞的指标。然而，在从相同组织中回收的 IgAVH 序列中，没有一个序列显示 B1a 细胞特异性。有趣的是，源自 L2 小鼠固有层的所有 IgAVH 序列均显示出大量核苷酸交换，表明体细胞超突变和亲和力成熟。这表明 B-1a 细胞对肠道免疫的天然未突变 IgA 的贡献可以忽略不计。
