title: Antigen-specific B lymphocytes acquire proteoglycan aggrecan from cartilage extracellular matrix resulting in antigen presentation and CD4+ T-cell activation.
abstract: The majority of studies examining antigen-presenting cell (APC) function have focused on the capture and presentation of antigens released from pathogens or damaged cells. However, antigen-specific B cells are also capable of efficiently extracting antigens that are either tethered to, or integrally part of the plasma membrane of various target cells. In this study we show that B cells are also highly efficient at extracting integral components of the extracellular matrix (ECM) for subsequent presentation. In particular we demonstrate that B cells specific for aggrecan, an integral component of cartilage ECM, acquire this rheumatoid arthritis candidate autoantigen in both a B-cell-receptor-dependent and a contact-dependent manner. We also demonstrate that the subsequent presentation of aggregan from ECM leads to CD4(+) T-cell activation and effector cell formation. Recent studies have identified B-cell-mediated antigen presentation as essential for the development of autoimmunity, but a unique role for B cells compared with other APC has yet to be defined. Our findings lead us to propose that the acquisition of ECM-derived autoantigens represents a mechanism that defines the APC requirement for B cells in the development of autoimmunity.
authors.affiliation: Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
authors.forename: Marzena
authors.initials: M
authors.lastname: Ciechomska
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Wilson
authors.forename: Achilleas
authors.initials: A
authors.lastname: Floudas
authors.forename: Wang
authors.initials: W
authors.lastname: Hui
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Rowan
authors.forename: Willem
authors.initials: W
authors.lastname: van Eden
authors.forename: John H
authors.initials: JH
authors.lastname: Robinson
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Knight
mesh_terms: D053674:Aggrecans / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002356:Cartilage / Q000276:immunology* / Q000473:pathology; D002417:Cattle; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation; D051379:Mice
chemical_list: D053674:Aggrecans; D001324:Autoantigens
keywords: B lymphocyte; CD4+ T lymphocyte; aggrecan; extracellular matrix; rheumatoid arthritis
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