title: The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B cells.
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.
authors.affiliation: Department of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Saulep-Easton
authors.affiliation: Department of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia.
authors.forename: F B
authors.initials: FB
authors.lastname: Vincent
authors.affiliation: Department of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia.
authors.forename: P S
authors.initials: PS
authors.lastname: Quah
authors.affiliation: Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia.|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.
authors.forename: A
authors.initials: A
authors.lastname: Wei
authors.affiliation: Department of Haematology, The Alfred Hospital, Melbourne, Victoria, Australia.|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.
authors.forename: S B
authors.initials: SB
authors.lastname: Ting
authors.affiliation: Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Croce
authors.affiliation: Department of Haematology, Peter MacCallum Cancer Centre, St. Andrews's Place, East Melbourne, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Tam
authors.affiliation: Department of Immunology, Monash University Central Clinical School, Alfred Medical Research and Education Precinct (AMREP), Melbourne, Victoria, Australia.
authors.forename: F
authors.initials: F
authors.lastname: Mackay
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000097:blood / Q000502:physiology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051217:Toll-Like Receptor 9 / Q000502:physiology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000502:physiology*
chemical_list: D053264:B-Cell Activating Factor; C486361:Tnfrsf13b protein, mouse; C505720:Tnfsf13b protein, mouse; D051217:Toll-Like Receptor 9; D053303:Transmembrane Activator and CAML Interactor Protein; D016753:Interleukin-10