Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China.
College of Pharmacy, Henan University, Kaifeng, China.
J Cell Mol Med. 2017 Dec;21(12):3658-3669. doi: 10.1111/jcmm.13276. Epub 2017 Jul 14.
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.
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发挥主要作用，并在自身免疫性疾病中过度激活。然而，MZ B 细胞发育的基本机制仍不清楚。我们在这里发现，CD19 缺陷阻止了边缘区前体（MZP）向 MZ B 细胞的分化，而在 CD19 缺陷的 MZP 中表达 CD19 可挽救 MZ B 细胞的生成。此外，CD19 通过上调 MZP 中的 ADAM28 表达来调节 Notch2 的切割。最后，我们发现 CD19 通过抑制 Foxo1 表达来促进 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 向 MZ B 细胞的分化。因此，我们证明了 MZP 向 MZ B 细胞分化的基本机制。
