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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Transcription factor ABF-1 suppresses plasma cell differentiation but facilitates memory B cell formation
Yi-Kai Chiu1, I-Ying Lin2, Shin-Tang Su3
1Genomics Research Center, Academia Sinica, Taipei 115, Taiwan; Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 112, Taiwan;
Abstract:
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.
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