The transcription factors IRF8 and PU.1 negatively regulate plasma cell differentiation Academic Article uri icon

abstract

  • Activated B cells undergo immunoglobulin class-switch recombination (CSR) and differentiate into antibody-secreting plasma cells. The distinct transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors: those that maintain the B cell program, including BCL6 and PAX5, and plasma cell-promoting factors, such as IRF4 and BLIMP-1. We show that the complex of IRF8 and PU.1 controls the propensity of B cells to undergo CSR and plasma cell differentiation by concurrently promoting the expression of BCL6 and PAX5 and repressing AID and BLIMP-1. As the PU.1-IRF8 complex functions in a reciprocal manner to IRF4, we propose that concentration-dependent competition between these factors controls B cell terminal differentiation.

authors

  • Carotta, Sebastian
  • Willis, Simon N
  • Hasbold, Jhagvaral
  • Inouye, Michael
  • Pang, Swee Heng Milon
  • Emslie, Dianne
  • Light, Amanda
  • Chopin, Michael
  • Shi, Wei
  • Wang, Hongsheng
  • Morse, Herbert C
  • Tarlinton, David M
  • Corcoran, Lynn M
  • Hodgkin, Philip D
  • Nutt, Stephen L

publication date

  • 2014