Universal expression and dual function of the atypical chemokine receptor D6 on innate-like B cells in mice

Hansell, C. A. H., Schiering, C., Kinstrie, R. , Ford, L., Bordon, Y., McInnes, I. B. , Goodyear, C. S. and Nibbs, R. J.B. (2011) Universal expression and dual function of the atypical chemokine receptor D6 on innate-like B cells in mice. Blood, 117(20), pp. 5413-5424. (doi:10.1182/blood-2010-11-317115) (PMID:21450903) (PMCID:PMC3188399)

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Publisher's URL: http://dx.doi.org/10.1182/blood-2010-11-317115

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 Ca2+ 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 classswitched 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. (Blood. 2011;117(20):5413-5424)

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Hansell, Dr Chris and Bordon, Miss Yvonne and Nibbs, Professor Robert and Kinstrie, Dr Ross and Goodyear, Professor Carl
Authors: Hansell, C. A. H., Schiering, C., Kinstrie, R., Ford, L., Bordon, Y., McInnes, I. B., Goodyear, C. S., and Nibbs, R. J.B.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Blood
Publisher:American Society of Hematology
ISSN:0006-4971
ISSN (Online):1528-0020
Published Online:30 March 2011

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514422Regulation of the adaptive immune response by chemokine scavenging receptorsGerard GrahamMedical Research Council (MRC)G0901113Infection Immunity and Inflammation Medicine