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

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 beta cells differentiate into PCs. Based on our observation that the expression of the transcription factor CCAAT/ enhancer binding protein beta (C/EBP beta) is associated with the emergence of post-switched PCs, we enquired whether a cell-autonomous function of C/EBP beta is involved in the program for PC development. To address this, we generated C/EPN-deficient mice in which the Cebpb locus was specifically deleted in B cells after transcription of the Ig gamma 1 constant gene segment (C gamma 1). In response to in vitro stimulation, B cells from these Cebpb(fl/fl)C gamma 1(Cre/+) 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 Cebpb(fl/fl)C gamma 1(Cre/+). 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/EPB beta is crucial for differentiation of post-switched GC B cells into PCs through a Blimpl-dependent pathway.