Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.
Oral-nasopharyngeal dendritic cells mediate T cell-independent IgA class switching on B-1 B cells.
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DOI：
10.1371/journal.pone.0025396
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Fujihashi K
中科院分区：
文献类型：
--
作者：
Kataoka K;Fujihashi K;Terao Y;Gilbert RS;Sekine S;Kobayashi R;Fukuyama Y;Kawabata S;Fujihashi K
天然霍乱毒素（nCT）作为鼻佐剂显示通过小鼠下颌下腺（SMG）和鼻通道（NP）中的CD 4 + T细胞和伊加+ B-1 B细胞之间的IL-5- IL-5受体相互作用引起T非依赖性S-IgA抗体（Ab）应答水平增加。在此，我们进一步研究口腔-鼻咽树突状细胞（DC）是否在诱导B-1 B细胞伊加类别转换重组（CSR）以增强T细胞非依赖性（TI）粘膜S-IgA Ab应答中发挥核心作用。与单独给予nCT或TNP-LPS的小鼠的相同组织相比，在从TCRβ−/−小鼠和野生型小鼠的SMG和NP纯化的B-1 B细胞上观察到活化诱导的胞苷脱氨酶、Iα-Cμ循环转录物和Iμ-Cα转录物的高表达水平。此外，来自给予鼻TNP-LPS + nCT的小鼠的SMG、NP和NALT的DC表达的增殖诱导配体（APRIL）水平显著高于单独给予TNP-LPS或nCT的小鼠中的增殖诱导配体（APRIL）水平，而SMG和NP中的B-1 B细胞显示出升高的跨膜激活剂和钙调节剂亲环蛋白配体相互作用物（TACI）表达水平。有趣的是，当腹膜伊加− IgM+ B细胞用来自给予鼻TNP-LPS加nCT的小鼠的粘膜DC刺激时，伊加+ B-1 B细胞的高频率被诱导。总之，这些发现表明鼻nCT通过与APRIL和TACI的相互作用在由B-1 B细胞增强粘膜DC介导的TI伊加CSR中起关键作用。
Native cholera toxin (nCT) as a nasal adjuvant was shown to elicit increased levels of T-independent S-IgA antibody (Ab) responses through IL-5- IL-5 receptor interactions between CD4+ T cells and IgA+ B-1 B cells in murine submandibular glands (SMGs) and nasal passages (NPs). Here, we further investigate whether oral-nasopharyngeal dendritic cells (DCs) play a central role in the induction of B-1 B cell IgA class switch recombination (CSR) for the enhancement of T cell-independent (TI) mucosal S-IgA Ab responses. High expression levels of activation-induced cytidine deaminase, Iα-Cμ circulation transcripts and Iμ-Cα transcripts were seen on B-1 B cells purified from SMGs and NPs of both TCRβ−/− mice and wild-type mice given nasal trinitrophenyl (TNP)-LPS plus nCT, than in the same tissues of mice given nCT or TNP-LPS alone. Further, DCs from SMGs, NPs and NALT of mice given nasal TNP-LPS plus nCT expressed significantly higher levels of a proliferation-inducing ligand (APRIL) than those in mice given TNP-LPS or nCT alone, whereas the B-1 B cells in SMGs and NPs showed elevated levels of transmembrane activator and calcium modulator cyclophilin ligand interactor (TACI) expression. Interestingly, high frequencies of IgA+ B-1 B cells were induced when peritoneal IgA− IgM+ B cells were stimulated with mucosal DCs from mice given nasal TNP-LPS plus nCT. Taken together, these findings show that nasal nCT plays a key role in the enhancement of mucosal DC-mediated TI IgA CSR by B-1 B cells through their interactions with APRIL and TACI.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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TACI和BAFF-R介导B细胞中的同种型切换。
影响因子：
15.3
作者：
Castigli, E;Wilson, SA;Scott, S;Dedeoglu, F;Xu, SL;Lam, KP;Bram, RJ;Jabara, H;Geha, RS
通讯作者：
Geha, RS