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Leukemia. 2016 Jan;30(1):163-72. doi: 10.1038/leu.2015.174. Epub 2015 Jul 3.

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

Author information

1
Department of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia.
2
Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia.
3
Australian Centre for Blood Diseases, Division of Blood Cancers, Department of Medicine, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia.
4
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA.
5
Department of Haematology, Peter MacCallum Cancer Centre, St. Andrews's Place, East Melbourne, Victoria, Australia.

Abstract

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.

PMID:
26139429
PMCID:
PMC4606984
DOI:
10.1038/leu.2015.174
[Indexed for MEDLINE]
Free PMC Article

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