IgA-producing plasma cells originate from germinal centers that are induced by B-cell receptor engagement in humans.
IgA-producing plasma cells originate from germinal centers that are induced by B-cell receptor engagement in humans.
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DOI：
10.1053/j.gastro.2010.12.005
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发表时间：
2011-03
期刊：
影响因子：
29.4
通讯作者：
Spencer J
中科院分区：
文献类型：
--
作者：
Barone F;Vossenkamper A;Boursier L;Su W;Watson A;John S;Dunn-Walters DK;Fields P;Wijetilleka S;Edgeworth JD;Spencer J
免疫球蛋白（IG）A有助于宿主和肠道微生物群之间的稳态平衡。启动伊加反应的机制尚不清楚，可能在人类和动物模型之间存在差异。我们使用多种实验方法来研究在胃肠道（GI）中产生伊加的人肠浆细胞的起源。通过对IG基因的分析，比较了人胃肠道粘膜和骨髓中产生IgA的浆细胞群的复杂性以及对口服霍乱疫苗的特异性应答。采用流式细胞术、基因表达分析和免疫组织化学分析了B细胞受体（BCR）参与人肠道相关淋巴组织（GALT）诱导的信号通路，并与非肠道部位相比，分析了GALT中先天免疫参与B细胞活化的情况。人肠道IgA产生的浆细胞似乎是生发中心的起源，没有证据表明，伴随着在骨髓中观察到的多个衍生途径的人口复杂性。在人GALT的生发中心B细胞中，Btk和Erk被磷酸化，CD 22被下调，林恩被易位到细胞膜，Fos和Jun被上调;这些特征表明生发中心进化期间BCR连接。与外周免疫区室相比，在GALT中未观察到B细胞的先天性激活差异。产生IgA的浆细胞似乎来源于人类的GALT生殖中心。BCR参与促进GALT生发中心的形成，与非肠道免疫区室相比，没有更多的证据表明粘膜中的先天免疫受体活化。GALT中的免疫中心应该是粘膜疫苗的靶点，因为它们是人肠道伊加反应的来源。
Immunoglobulin (Ig)A contributes to the homeostatic balance between host and the intestinal microbiota. Mechanisms that initiate the IgA response are unclear and likely to differ between humans and animal models. We used multiple experimental approaches to investigate the origin of the human intestinal plasma cells that produce IgA in the gastrointestinal (GI) tract. The complexity of IgA-producing plasma cell populations in human GI mucosa and bone marrow and the specific response to oral cholera vaccine were compared by analysis of Ig genes. Flow cytometry, gene expression analysis, and immunohistochemistry were used to analyze signaling pathways induced by B-cell receptor (BCR) engagement in human gut-associated lymphoid tissue (GALT) and the involvement of innate immunity in B-cell activation in GALT, compared with non-intestinal sites. Human intestinal IgA-producing plasma cells appeared to be of germinal center origin; there was no evidence for the population complexity that accompanies the multiple pathways of derivation observed in bone marrow. In germinal center B cells of human GALT, Btk and Erk are phosphorylated, CD22 is downregulated, Lyn is translocated to the cell membrane, and Fos and Jun are upregulated; these features indicate BCR ligation during germinal center evolution. No differences in innate activation of B cells were observed in GALT, compared with peripheral immune compartments. IgA-producing plasma cells appear to be derived from GALT germinal centers in humans. BCR engagement promotes formation of germinal centers of GALT, with no more evidence for innate immune receptor activation in the mucosa than non-intestinal immune compartments. Germinal centers in GALT should be the targets of mucosal vaccinations because they are the source of the human intestinal IgA response.
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在聚合物免疫球蛋白受体/分泌成分缺陷的小鼠中，缺乏上皮免疫球蛋白A转运，粘膜泄漏增加。
影响因子：
15.3
作者：
Johansen, F E;Pekna, M;Norderhaug, I N;Haneberg, B;Hietala, M A;Krajci, P;Betsholtz, C;Brandtzaeg, P
通讯作者：
Brandtzaeg, P
影响因子：
5.4
作者：
DunnWalters, DK;Boursier, L;Spencer, J
通讯作者：
Spencer, J
影响因子：
3.6
作者：
Halcomb, Kristina E.;Musuka, Sandirai;Satterthwaite, Anne B.
通讯作者：
Satterthwaite, Anne B.
影响因子：
7.1
作者：
WALKER, WA;ISSELBACHER, KJ;BLOCH, KJ
通讯作者：
BLOCH, KJ
影响因子：
56.9
作者：
Fagarasan, S;Muramatsu, M;Honjo, T
通讯作者：
Honjo, T