BCAP 通过 c-Rel 对成熟 B 细胞维持的贡献。

Contribution of BCAP to maintenance of mature B cells through c-Rel.

作者信息

Yamazaki Tetsuo, Kurosaki Tomohiro

机构信息

Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan.

出版信息

Nat Immunol. 2003 Aug;4(8):780-6. doi: 10.1038/ni949. Epub 2003 Jun 29.

DOI:10.1038/ni949

PMID:12833156

Abstract

Mice deficient in the B cell adaptor for phosphoinositide 3-kinase (BCAP) have reduced numbers of mature B lymphocytes, which show defects in cell survival and proliferation. We found here that the NF-kappa B (Rel) pathway was impaired in BCAP-deficient mature B cells and that NF-kappa B target genes, indispensable for cell survival and division, were not induced in response to B cell receptor (BCR) stimulation. Among the NF-kappa B (Rel) family, expression of c-Rel was specifically reduced in BCAP-deficient B cells. Retrovirus-mediated reintroduction of c-Rel restored the pool size of immunoglobulin (Ig)M(lo)IgD(hi) mature B cells in the spleen as well as proliferative responses to BCR stimulation. These results indicate BCAP is essential in the maintenance of mature B cells through functional coupling with c-Rel.

摘要

缺乏磷酸肌醇3激酶（PI3K）的B细胞衔接蛋白（BCAP）的小鼠，其成熟B淋巴细胞数量减少，这些细胞在细胞存活和增殖方面存在缺陷。我们在此发现，BCAP缺陷的成熟B细胞中NF-κB（Rel）信号通路受损，并且对细胞存活和分裂必不可少的NF-κB靶基因在B细胞受体（BCR）刺激下未被诱导。在NF-κB（Rel）家族中，c-Rel的表达在BCAP缺陷的B细胞中特异性降低。逆转录病毒介导的c-Rel重新引入恢复了脾脏中免疫球蛋白（Ig）M（低）IgD（高）成熟B细胞的库大小以及对BCR刺激的增殖反应。这些结果表明，BCAP通过与c-Rel的功能偶联，对成熟B细胞的维持至关重要。