Antigen‐specific B lymphocytes acquire proteoglycan aggrecan from cartilage extracellular matrix resulting in antigen presentation and CD4+ T‐cell activation

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.