IgA and IgM VH repertoires in human colon:: Evidence for clonally expanded B cells that are widely disseminated
IgA and IgM VH repertoires in human colon:: Evidence for clonally expanded B cells that are widely disseminated
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DOI：
10.1053/gast.2000.20219
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发表时间：
2000-11-01
期刊：
影响因子：
29.4
通讯作者：
Caspary, WF
中科院分区：
文献类型：
--
作者：
Holtmeier, W;Hennemann, A;Caspary, WF
背景与目的：粘膜免疫系统保护机体免受粘膜表面持续暴露的病原体的侵害。由于固有层B细胞应反映肠道的抗原经验，我们研究了它们的免疫球蛋白（IG）库和分布。研究方法：通过CDR 3大小谱和核苷酸测序分析了健康成人结肠和外周血中伊加和IgM重链转录本的连接多样性。结果如下：肠伊加和IgM细胞的V（H）6和V（H）7库是寡克隆的，而较大的V（H）1-V（H）5家族的CDR 3谱表明具有叠加在多克隆背景上的优势条带的更多样的库。然而，序列分析显示多个重复和克隆相关的转录本在遥远的结肠网站从所有V-H家族。这表明，除了多克隆B细胞池，B细胞亚群克隆扩增并沿沿着结肠广泛分布。偶尔，有证据表明B细胞具有相同的CDR 3特异性，其表现出从IgM到伊加的同种型转换。循环中的伊加B细胞表达一种与结肠中不同的限制性V-H谱。结论：人类结肠含有广泛分布的表达克隆相关的伊加或IgM受体的B细胞。这些结果最好用抗原驱动的过程来解释，其中肠记忆B细胞持续再循环。
Background & Aims: The mucosal immune system defends the body from pathogens to which the mucosal surfaces are continually exposed. Because lamina propria B cells should reflect the antigenic experience of the gut, we investigated their immunoglobulin (Ig) repertoire and distribution. Methods: The junctional diversity of the IgA and IgM heavy-chain transcripts in the colon and the peripheral blood of healthy adults was analyzed by CDR3 size spectratyping and nucleotide sequencing. Results: The V(H)6 and V(H)7 repertoires of intestinal IgA and IgM cells were oligoclonal, whereas the CDR3 profiles of the larger V(H)1-V(H)5 families suggested a more diverse repertoire with dominant bands superimposed on a polyclonal background. However, sequence analysis revealed multiple repetitive and clonally related transcripts at distant colonic sites from all V-H families. This suggests that, in addition to a polyclonal B-cell pool, subsets of B cells are clonally expanded and widely distributed along the colon. Occasionally, there was evidence for B cells with the same CDR3 specificity, which exhibited an isotype switch from IgM to IgA. Circulating IgA B cells expressed a restricted V-H repertoire that was distinct from that in the colon. Conclusions: The human colon contains widely disseminated B cells that express clonally related IgA or IgM receptors. These results are best explained by an antigen-driven process whereby intestinal memory B cells continuously recirculate.