1] Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden [2] State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
Mucosal Immunol. 2014 May;7(3):511-20. doi: 10.1038/mi.2013.68. Epub 2013 Sep 25.
Human immunoglobulin A (IgA) comprises two IgA subclasses, IgA1 and IgA2, whose distribution has been shown by immunohistochemistry to be different in various body compartments. In comparison with systemic immune compartments, we investigated the IgA switch profiles at the molecular level in salivary and lacrimal glands, nasal mucosa, and proximal and distal gut mucosa. Direct switching from IgM to IgA1 or IgA2 predominated in all immune compartments analyzed. Similar composition of the Sμ-Sα1 and Sμ-Sα2 junctions was observed, including microhomology usage, which suggested that there is no major difference in the actual recombination mechanism utilized during IgA subclass switching. The proportion of IgA1/IgA2 switch recombination events largely paralleled the previously published immunohistochemical representation of IgA1(+) and IgA2(+) plasma cells, implying that the local subclass distribution generally reflects precommitted memory/effector B cells that have undergone IgA subclass switching before extravasation at the effector site. The extremely low or undetectable levels of activation-induced cytidine deaminase (AID) and Iα-Cμ circle transcripts in intestinal lamina propria samples as compared with Peyer's patches suggest that the cellular IgA subclass distribution outside of organized gut-associated lymphoid tissue is only to a minor extent, if at all, influenced by in situ switching.
人类免疫球蛋白 A（IgA）包括两个 IgA 亚类，IgA1 和 IgA2，其分布已通过免疫组织化学显示在不同的身体部位不同。与全身免疫部位相比，我们在唾液腺和泪腺、鼻黏膜以及近端和远端肠道黏膜中从分子水平研究了 IgA 转换谱。直接从 IgM 转换为 IgA1 或 IgA2 在所有分析的免疫部位中占主导地位。观察到 Sμ-Sα1 和 Sμ-Sα2 接头的相似组成，包括微同源性的使用，这表明在 IgA 亚类转换过程中实际使用的重组机制没有重大差异。IgA1/IgA2 转换重组事件的比例与先前发表的 IgA1(+)和 IgA2(+)浆细胞的免疫组织化学表示大致平行，这意味着局部亚类分布通常反映了在效应部位外渗之前已经经历过 IgA 亚类转换的预先承诺的记忆/效应 B 细胞。与派尔斑相比，肠固有层样本中激活诱导的胞苷脱氨酶（AID）和 Iα-Cμ 环转录本的极低或无法检测水平表明，在未组织化的肠道相关淋巴组织之外，细胞 IgA 亚类分布仅在一定程度上受到原位转换的影响，如果有的话。
