CD19 regulates ADAM28-mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells.

CD19 regulates ADAM28-mediated Notch2 cleavage to control the differentiation of marginal zone precursors to MZ B cells.
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CD19 调节 ADAM28 介导的 Notch2 裂解,以控制边缘区前体细胞向 MZ B 细胞的分化。

DOI:
10.1111/jcmm.13276
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发表时间:
2017-12
影响因子:
5.3
通讯作者:
Wang R
Wang R
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Y;Zhu G;Xiao H;Liu X;Han G;Chen G;Hou C;Shen B;Li Y;Ma N;Wang R

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作为第一道防线,边缘区(MZ) B细胞在感染期间清除血源性病原体中起主要作用,并且在自身免疫性疾病中被过度激活。然而,MZ B细胞发育的基本机制尚不清楚。我们在这里发现,CD19缺乏阻断了边缘区前体(MZP)向MZ B细胞的分化,而CD19在CD19缺乏的MZP中的表达可以挽救MZ B细胞的生成。此外,CD19通过上调MZP中ADAM28的表达来调节Notch2的切割。最后,我们发现CD19抑制Foxo1的表达,促进了MZP中ADAM28的表达。这些结果表明,CD19通过调节ADAM28介导的Notch2切割来控制MZP细胞向mzb细胞的分化。因此,我们证明了MZP向mzb细胞分化的基本机制。
As the first line of defence, marginal zone (MZ) B cells play principal roles in clearing blood‐borne pathogens during infection and are over‐primed in autoimmune diseases. However, the basic mechanisms underlying MZ B‐cell development are still unclear. We found here that CD19 deficiency blocked the differentiation of marginal zone precursors (MZP) to MZ B cells, whereas CD19 expression in CD19‐deficient MZP rescues MZ B‐cell generation. Furthermore, CD19 regulates Notch2 cleavage by up‐regulating ADAM28 expression in MZP. Finally, we found that CD19 suppressed Foxo1 expression to promote ADAM28 expression in MZP. These results suggest that CD19 controls the differentiation of MZP to MZ B cells by regulating ADAM28‐mediated Notch2 cleavage. Thus, we demonstrated the basic mechanisms underlying the differentiation of MZP to MZ B cells.
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