B cell ADAM17 controls T cell independent humoral immune responses through regulation of TACI and CD138
B cell ADAM17 controls T cell independent humoral immune responses through regulation of TACI and CD138
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DOI：
10.1016/j.bbrc.2019.11.124
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发表时间：
2020-02-05
影响因子：
3.1
通讯作者：
Martin, Rebecca K.
中科院分区：
文献类型：
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作者：
Lownik, Joseph C.;Wimberly, Jessica L.;Martin, Rebecca K.
已知ADAM17通过释放肿瘤坏死因子α(TNFα)对免疫系统做出贡献。然而，ADAM17在B细胞生物学中的作用还没有得到很好的描述。为了确定B细胞ADAM17是否参与T细胞非依赖性体液免疫反应，我们将CD19Cre转基因小鼠与携带ADAM17等位基因的小鼠(ADAM17(CD)(19))进行杂交。在这项研究中，我们展示了ADAM17在调节小鼠边缘带B细胞(MZB)数量方面的内在作用。有趣的是，我们证明了B细胞ADAM17的缺失导致了初始状态和T细胞非依赖性抗原免疫后MZB数量的减少，但增强了对T细胞非依赖性抗原的体液免疫。此外，我们还发现ADAM17(CD19)小鼠免疫后浆细胞上TACI和CD138水平升高。总体而言，这些发现表明B细胞ADAM17可能通过MZB数量和血浆细胞抗体的产生来协调T细胞非依赖性免疫反应。(C)2019 Elsevier Inc.保留所有权利。
ADAM17 is known to contribute to the immune system through its shedding of tumor necrosis factor alpha (TNF alpha). However, the role of ADAM17 in B cell biology is not well characterized. To determine whether B cell ADAM17 contributes to T cell-independent humoral immune responses, we crossed CD19 Cre transgenic mice with mice bearing a floxed allele of ADAM17 (ADAM17(CD)(19)). In this study, we show a B cell intrinsic role for ADAM17 in regulating marginal zone B cell (MZB) numbers in mice. Interestingly, we demonstrate that the loss of B cell ADAM17 results in reduced MZB numbers in the naive state and after immunization with T-independent antigen, yet enhanced humoral immunity to T cell independent antigens. We additionally find elevated TACI and CD138 levels on plasma cells following immunization in ADAM17(CD19) mice. Overall, these findings suggest that B cell ADAM17 may orchestrate T independent immune responses through both MZB numbers and plasma cell antibody production. (C) 2019 Elsevier Inc. All rights reserved.