TIM-1 signaling in B cells regulates antibody production
TIM-1 signaling in B cells regulates antibody production
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DOI：
10.1016/j.bbrc.2011.02.021
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发表时间：
2011-03-11
影响因子：
3.1
通讯作者：
Akiba, Hisaya
中科院分区：
文献类型：
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作者：
Ma, Juan;Usui, Yoshihiko;Akiba, Hisaya
T细胞免疫球蛋白和粘蛋白(TIM)家族的成员最近被认为参与了T细胞介导的免疫反应的控制。在这项研究中，我们发现TIM-1在抗IgM或抗CD40刺激的脾B细胞上的表达，在抗LGM和抗CD40抗体的联合作用下进一步上调。另一方面，TIM-1配体在B细胞上结构性表达，并在抗CD3(+)抗CD28刺激的CD4(+)T细胞上诱导表达。在体外，抗TIM-1单抗刺激活化的B细胞，促进其增殖和浆细胞标志物Syndecan-1(CD138)的表达。我们进一步研究了TIM-1信号对体外和体内抗体产生的影响。抗TIM-1刺激的B细胞培养上清液中的IgG2b和IgG3分泌水平均高于对照组。用T非依赖性抗原TNP-Ficoll免疫后，抗TIM-1处理的小鼠的TNP特异性IgG1、IgG2b和IgG3Abs略有增加。经T依赖抗原OVA免疫后，抗TIM-1组小鼠血清中OVA特异性IgG2b、IgG3和IgE抗体水平显著高于对照组(P<0.05)。这些结果表明，B细胞中的TIM-1信号通过促进B细胞的增殖和分化而增加抗体的产生。(C)2011 Elsevier Inc.保留所有权利。
Members of the T cell Ig and mucin (TIM) family have recently been implicated in the control of T cell-mediated immune responses. In this study, we found TIM-1 expression on anti-IgM- or anti-CD40-stimulated splenic B cells, which was further up-regulated by the combination of anti-lgM and anti-CD40 Abs. On the other hand, TIM-1 ligand was constitutively expressed on B cells and inducible on anti-CD3(+) anti-CD28-stimulated CD4(+) T cells. In vitro stimulation of activated B cells by anti-TIM-1 mAb enhanced proliferation and expression of a plasma cell marker syndecan-1 (CD138). We further examined the effect of TIM-1 signaling on antibody production in vitro and in vivo. Higher levels of IgG2b and IgG3 secretion were detected in the culture supernatants of the anti-TIM-1-stimulated B cells as compared with the control IgG-stimulated B cells. When immunized with T-independent antigen TNP-Ficoll, TNP-specific IgG1, IgG2b, and IgG3 Abs were slightly increased in the anti-TIM-1-treated mice. When immunized with T-dependent antigen OVA, serum levels of OVA-specific IgG2b, IgG3, and IgE Abs were significantly increased in the anti-TIM-1-treated mice as compared with the control IgG-treated mice. These results suggest that TIM-1 signaling in B cells augments antibody production by enhancing B cell proliferation and differentiation. (C) 2011 Elsevier Inc. All rights reserved.