title: Universal expression and dual function of the atypical chemokine receptor D6 on innate-like B cells in mice.
abstract: Mouse innate-like B cells are a heterogeneous collection of multifunctional cells that control infection, play housekeeping roles, contribute to adaptive immunity, and suppress inflammation. We show that, among leukocytes, chemokine internalization by the D6 receptor is a unique and universal feature of all known innate-like B-cell populations and, to our knowledge, the most effective unifying marker of these cells. Moreover, we identify novel D6(active) B1-cell subsets, including those we term B1d, which lack CD5 and CD11b but exhibit typical B1-cell properties, including spontaneous ex vivo production of IgM, IL-10, and anti-phosphorylcholine antibody. The unprecedented opportunity to examine D6 on primary cells has allowed us to clarify its ligand specificity and show that, consistent with a scavenging role, D6 internalizes chemokines but cannot induce Ca(2+) fluxes or chemotaxis. Unexpectedly, however, D6 can also suppress the function of CXCR5, a critical chemokine receptor in innate-like B-cell biology. This is associated with a reduction in B1 cells and circulating class-switched anti-phosphorylcholine antibody in D6-deficient mice. Therefore, in the present study, we identify a unifying marker of innate-like B cells, describe novel B1-cell subsets, reveal a dual role for D6, and provide the first evidence of defects in resting D6-deficient mice.
authors: Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow, United Kingdom.
authors: Chris A H
authors: CA
authors: Hansell
authors: Chris
authors: C
authors: Schiering
authors: Ross
authors: R
authors: Kinstrie
authors: Laura
authors: L
authors: Ford
authors: Yvonne
authors: Y
authors: Bordon
authors: Iain B
authors: IB
authors: McInnes
authors: Carl S
authors: CS
authors: Goodyear
authors: Robert J B
authors: RJ
authors: Nibbs
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D039481:CD11b Antigen / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D020013:Calcium Signaling / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D005260:Female; D007113:Immunity, Innate; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009852:Omentum / Q000166:cytology / Q000276:immunology; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D017455:Receptors, IgE / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D000097628:Chemokine Receptor D6
chemical_list: D039481:CD11b Antigen; D018956:CD5 Antigens; D018925:Chemokines; D019707:Receptors, Chemokine; D017455:Receptors, IgE; C515709:Ackr2 protein, mouse; D000097628:Chemokine Receptor D6; C526836:Cd5 protein, mouse