Distinct roles of BCNP1 in B-cell development and activation
Distinct roles of BCNP1 in B-cell development and activation
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DOI：
10.1093/intimm/dxz055
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发表时间：
2020-01-01
影响因子：
4.4
通讯作者：
Wang，Ji-Yang
中科院分区：
文献类型：
--
作者：
Hong，Rongjian;Lai，Nannan;Wang，Ji-Yang
B细胞新型蛋白1（BCNP1）最近被鉴定为一种新的B细胞受体（BCR）信号分子，但其生理功能仍不清楚。在这里，我们证明缺乏 BCNP1 的小鼠表现出 B 细胞成熟受损和 B-1a 细胞减少。与野生型脾 B 细胞相比，BCNP1 缺陷型脾 B 细胞在响应 BCR 交联时表现出更高的存活率、增殖能力和 Ca2+ 内流。一致地，突变 B 细胞在 BCR 交联后表现出 SYK、B 细胞连接蛋白 (BLNK) 和 PLCγ2 的磷酸化升高。在体内，BCNP1 缺陷小鼠表现出对 T 非依赖性和 T 依赖性抗原的体液免疫应答增强。此外，老年突变小鼠的血清 IgM 和 IgG3 抗体水平升高，并在淋巴器官中表现出多克隆和单克隆 B 细胞扩增。这些结果揭示了 BCNP1 在 B 细胞发育、激活和稳态中的独特作用。
B-cell novel protein 1 (BCNP1) has recently been identified as a new B-cell receptor (BCR) signaling molecule but its physiological function remains unknown. Here, we demonstrate that mice deficient in BCNP1 exhibit impaired B-cell maturation and a reduction of B-1a cells. BCNP1-deficient spleen B cells show enhanced survival, proliferation and Ca2+influx in response to BCR cross-linking as compared with wild-type spleen B cells. Consistently, mutant B cells show elevated phosphorylation of SYK, B-cell linker protein (BLNK) and PLCγ2 upon BCR cross-linking.In vivo, BCNP1-deficient mice exhibit enhanced humoral immune responses to T-independent and T-dependent antigens. Moreover, aged mutant mice contain elevated levels of serum IgM and IgG3antibodies and exhibit polyclonal and monoclonal B-cell expansion in lymphoid organs. These results reveal distinct roles for BCNP1 in B-cell development, activation and homeostasis.