Transcription Factor ABF-1 Suppresses Plasma Cell Differentiation but Facilitates Memory B Cell Formation

被引:25
作者
Chiu, Yi-Kai [1 ,2 ]
Lin, I-Ying [1 ,3 ]
Su, Shin-Tang [1 ]
Wang, Kuan-Hsiung [1 ,4 ]
Yang, Shii-Yi [1 ]
Tsai, Dong-Yan [1 ,3 ]
Hsieh, Yi-Ting [1 ]
Lin, Kuo-I [1 ,2 ,3 ,4 ]
机构
[1] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan
[2] Natl Yang Ming Univ, Inst Microbiol & Immunol, Taipei 112, Taiwan
[3] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 112, Taiwan
[4] Natl Taiwan Univ, Inst Immunol, Taipei 110, Taiwan
关键词
PROTEIN-A; BLIMP-1; GENE; FLI-1; EXPRESSION; PROLIFERATION; ANTIBODY; ABSENCE; BINDING; BCL6;
D O I
10.4049/jimmunol.1400411
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ag-primed B cells that result from an immune response can form either memory B cells or Ab-secreting plasma cells; however, the molecular machinery that controls this cellular fate is poorly understood. In this study, we show that activated B cell factor-1 (ABF-1), which encodes a basic helix-loop-helix transcriptional repressor, participates in this regulation. ABF-1 was prevalently expressed in purified memory B cells and induced by T follicular helper cell mediated signals. ABF-1 expression declined by the direct repression of B lymphocyte induced maturation protein-1 during differentiation. Ectopic expression of ABF-1 reduced the formation of Ab-secreting cells in an in vitro differentiation system of human memory B cells. Accordingly, knockdown of ABF-1 potentiates the formation of Ab-secreting cells. A transgenic mouse that expresses inducible ABF-1 in a B cell-specific manner was generated to demonstrate that the formation of germinal center and memory B cells was augmented by induced ABF-1 in an immune response, whereas the Ag-specific plasma cell response was dampened. This effect was associated with the ability of ABF-1 to limit cell proliferation. Together, our results demonstrate that ABF-1 facilitates formation of memory B cells but prevents plasma cell differentiation.
引用
收藏
页码:2207 / 2217
页数:11
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