IL-6 Triggers IL-21 production by human CD4 T cells to drive STAT3-dependent plasma cell differentiation in B cells

摘要

Interleukin (IL)-21-producing CD4 T cells are central to humoral immunity. Deciphering the signals that induce IL-21 production in CD4 T cells and those triggered by IL-21 in B cells are, therefore, of importance for understanding the generation of antibody (Ab) responses. Here, we show that IL-6 increased IL-21 production by human CD4 T cells, particularly in those that express the transcriptional regulator B cell lymphoma (BCL)6, which is required in mice for the development of C-X-C chemokine receptor type 5 (CXCR5 ) IL-21-producing T follicular helper (T FH) cells. However, retroviral overexpression of BCL6 in total human CD4 T cells only transiently increased CXCR5, the canonical T FH -defining surface marker. We show here that IL-21 was required for the induction of Ab production by IL-6. In IL-21-treated B cells, signal transducer and activator of transcription (STAT)3 was required for optimal immunoglobulin production and upregulation of PR domain containing 1 (PRDM1 ), the master plasma cell factor. These results, therefore, demonstrate the critical importance of STAT3 activation in B cells during IL-21-driven humoral immunity and suggest that BCL6 expression, although not sufficient, may serve as a platform for the acquisition of a T FH -like phenotype by human CD4 T cells.