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CCAAT/enhancer binding protein β Induces Post-Switched B Cells to Produce Blimp1 and Differentiate into Plasma Cells

  • Geonhee Lee (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Eunkyeong Jang (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University) ;
  • Jeehee Youn (Laboratory of Autoimmunology, Department of Anatomy and Cell Biology, College of Medicine, Hanyang University)
  • Received : 2020.04.14
  • Accepted : 2020.08.26
  • Published : 2020.10.31
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Abstract

Long-lasting post-switched plasma cells (PCs) arise mainly from germinal center (GC) reactions, but little is known about the mechanism by which GC B cells differentiate into PCs. Based on our observation that the expression of the transcription factor CCAAT/enhancer binding protein β (C/EPBβ) is associated with the emergence of post-switched PCs, we enquired whether a cell-autonomous function of C/EPBβ is involved in the program for PC development. To address this, we generated C/EPBβ-deficient mice in which the Cebpb locus was specifically deleted in B cells after transcription of the Ig γ1 constant gene segment (Cγ1). In response to in vitro stimulation, B cells from these Cebpbfl/flCγ1Cre/+ mice had defects in the induction of B lymphocyte-induced maturation protein 1 (Blimp1) and the formation of IgG1+ PCs, but not in proliferation and survival. At steady state, the Cebpbfl/flCγ1Cre/+ mice had reduced serum IgG1 titers but normal IgG2c and IgM titers. Moreover, upon immunization with T-dependent Ag, the mice produced reduced levels of Ag-specific IgG1 Ab, and were defective in the production of Ag-specific IgG1 Ab-secreting cells. These results suggest that a cell-autonomous function of C/EPBβ is crucial for differentiation of post-switched GC B cells into PCs through a Blimp1-dependent pathway.

Keywords

Acknowledgement

We thank Mr. Changyeon Kim for technical assistance and the Analytical Instrumentation Center (Seoul) at Hanyang University for technical support. This work was supported by a grant from National Research Foundation of Korea (NRF-2018R1A2B6004853).

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