IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut

IgA class switch occurs in the organized nasopharynx- and gut-associated lymphoid tissue, but not in the diffuse lamina propria of airways and gut
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DOI:
10.4049/jimmunol.172.10.6259
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发表时间:
2004-05-15
影响因子:
4.4
通讯作者:
Kiyono, H
Kiyono, H
中科院分区:
医学2区
文献类型:
--
作者:
Shikina, T;Hiroi, T;Kiyono, H

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分泌型IgA作为机体免疫的第一道防线,在机体免疫反应中起着至关重要的作用。最近在肠道固有层进行的原位免疫球蛋白A类转换的证明为重新考虑免疫球蛋白A承诺的B细胞归巢的模型提供了机会,该模型的特征是不同的转运模式到效应部位。这些效应部位依赖于有组织的粘膜相关淋巴组织作为它们的诱导部位。在这篇报道中,我们发现在有组织的粘膜相关淋巴组织中,如鼻咽相关淋巴组织、分离的淋巴滤泡和Peyer‘s补片中,属于IgA同型转换细胞前和后的IgM(+)B220(+)和IgA(+)B220(+)细胞优先存在,而在弥漫效应组织中,如鼻道和肠道固有层,这些细胞群存在缺陷。与这些发现一致的是,在这些有组织的粘膜相关淋巴结构中选择性地检测到一系列与IgA同型转换重组相关的分子的表达,包括激活诱导的胞苷脱氨酶、Ipha-CMU环转录本和Ipha-CMU环转录本,但在弥漫的粘膜效应部位没有检测到。综上所述,这些发现表明,IgA亚型转换只发生在有组织的粘膜相关淋巴器官(如鼻咽相关淋巴组织、分离的淋巴滤泡和Peyer‘s斑块),而不是在上呼吸道和胃肠道的弥漫效应组织中。
Secretory IgA plays a crucial role in the host immune response as a first line of defense. A recent demonstration of in situ IgA class switching in intestinal lamina propria provided an opportunity to reconsider the model for the homing of IgA-committed B cells characterized by distinctive trafficking patterns to effector sites. Those effector sites depend on the organized mucosa-associated lymphoid tissues as their site of induction. In this report we show the preferential presence of IgM(+)B220(+) and IgA(+)B220(+) cells belonging to pre- and post-IgA isotype class-switched cells in the organized mucosa-associated lymphoid tissues, such as nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches, and the defect of those populations in the diffuse effector tissues, such as the nasal passage and intestinal lamina propria. Consistent with these findings, the expressions of a series of IgA isotype class switch recombination-related molecules, including activation-induced cytidine deaminase, Ialpha-Cmu circle transcripts, and Ialpha-Cmu circle transcripts, were selectively detected in these organized mucosa-associated lymphoid structures, but not in the diffuse mucosal effector sites. Taken together, these findings suggest that IgA isotype class switching occurs only in the organized mucosa-associated lymphoid organs (e.g., nasopharynx-associated lymphoid tissues, isolated lymphoid follicles, and Peyer's patches), but not in the diffuse effector tissues of the upper respiratory and gastrointestinal tracts.