Transcription factor ABF-1 suppresses plasma cell differentiation but facilitates memory B cell formation

J Immunol. 2014 Sep 1;193(5):2207-17. doi: 10.4049/jimmunol.1400411. Epub 2014 Jul 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Proliferation*
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunologic Memory*
  • Mice
  • Mice, Transgenic
  • Plasma Cells / cytology
  • Plasma Cells / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*

Substances

  • Transcription Factors