BANK negatively regulates Akt activation and subsequent B cell responses

被引：91

作者：

Aiba, Y

Yamazaki, T

Okada, T

Gotoh, K

Sanjo, H

Ogata, M

Kurosaki, T ^{[1
]}

机构：

[1] RIKEN, Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan

[2] Kansai Med Univ, Dept Mol Genet, Inst Liver Res, Moriguchi, Osaka 5708506, Japan

[3] Mie Univ, Sch Med, Dept Biochem, Tsu, Mie 5148507, Japan

来源：

IMMUNITY | 2006年 / 24卷 / 03期

关键词：

D O I：

10.1016/j.immuni.2006.01.002

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

BANK is an adaptor protein that is highly expressed in B cells. To investigate its physiological role, we generated BANK-deficient mice. BANK-deficient mice displayed enhanced germinal center formation and IgM production in response to T-dependent antigens, whereas this phenotype was blocked in CD40-BANK double knockout mice. Involvement of BANK in CD40 signaling was further demonstrated by in vitro analysis. CD40-mediated proliferation and survival were significantly increased in BANK-deficient B cells, with enhanced Akt activation, whereas introduction of dominant-negative Akt into BANK-deficient B cells suppressed the augmented CD40-mediated responses. Together, our findings suggest that BANK attenuates CD40-mediated Akt activation, thereby preventing hyperactive B cell responses.

引用

页码：259 / 268

页数：10

共 46 条

[1] Resolution of three nonproliferative immature splenic B cell subsets reveals multiple selection points during peripheral B cell maturation [J].