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The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells

2015; Springer Nature; Volume: 30; Issue: 1 Linguagem: Inglês

10.1038/leu.2015.174

1476-5551

Damien Saulep-Easton, Fabien B. Vincent, Pin Shie Quah, Andrew H. Wei, Stephen B. Ting, C. M. Croce, Constantine S. Tam, Fabienne Mackay,

Immune Cell Function and Interaction

Interleukin (IL)-10-producing B cells (B10 cells) have emerged as important regulatory elements with immunosuppressive roles. Chronic lymphocytic leukemia (CLL) B cells also secrete IL-10 and share features of B10 cells, suggesting a possible contribution of CLL B cells to immunosuppression in CLL patients. Factors controlling the emergence of B10 cells are not known. B-cell-activating factor of the tumor necrosis factor (TNF) family (BAFF) is critical for B-cell maturation and survival, and is implicated in the development and progression of CLL. We sought to investigate the role of BAFF in the emergence of IL-10-producing regulatory B cells in healthy donors and CLL patients. Here, we report that BAFF signaling promotes IL-10 production by CLL B cells in a mouse model of CLL and in CLL patients. Moreover, BAFF-mediated IL-10 production by normal and CLL B cells is mediated via its receptor transmembrane activator and cyclophilin ligand interactor. Our work uncovered a major targetable pathway important for the generation of regulatory B cells that is detrimental to immunity in CLL.