title: BAFF costimulation of Toll-like receptor-activated B-1 cells.
abstract: B cell-activating factor belonging to the TNF family (BAFF) and its receptor BAFF-R play critical roles in the maturation and survival of conventional peripheral B cells. However, they appeared to be dispensable for the generation and maintenance of CD5(+) B-1 cells as BAFF(-/-) and BAFF-R(-/-) mice have normal B-1 cell populations. Hence, it is presently unclear if B-1 cells are responsive to BAFF and if BAFF regulates some aspects of B-1 cell function. We show here that BAFF-R and transmembrane activator and CAML interactor (TACI) are the major receptors expressed by B-1 cells. Specifically, we show that BAFF treatment of B-1 cells leads to increased NF-kappaB p100 processing and CD21/CD35 expression. Interestingly, toll-like receptor (TLR) engagement of B-1 cells augmented the surface expression of BAFF receptors and rendered them responsive to BAFF costimulation, as evidenced by their increased proliferation, expression of cell surface activation markers and secretion of the pro-inflammatory cytokine IL-6 and the anti-inflammatory cytokine IL-10. This costimulatory effect is achieved primarily through BAFF-R as BAFF failed to costimulate B-1 cells obtained from A/WySnJ mice which have defective BAFF-R signaling. Thus, as TLR are innate immune receptors and B-1 cells are "innate-like" lymphocytes, our data provide evidence that BAFF plays a role in innate immunity.
authors.affiliation: Laboratory of Immunology, Center for Molecular Medicine and Institute of Molecular and Cell Biology, Singapore.
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.forename: Chee-Hoe
authors.initials: CH
authors.lastname: Ng
authors.forename: Blanche
authors.initials: B
authors.lastname: Woehl
authors.forename: Andrew P R
authors.initials: AP
authors.lastname: Sutherland
authors.forename: Jianxin
authors.initials: J
authors.lastname: Huo
authors.forename: Shengli
authors.initials: S
authors.lastname: Xu
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D051193:Toll-Like Receptors / Q000502:physiology*; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000502:physiology*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C486361:Tnfrsf13b protein, mouse; C486662:Tnfrsf13c protein, mouse; C490176:Tnfrsf17 protein, mouse; C505720:Tnfsf13b protein, mouse; D051193:Toll-Like Receptors; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha