期刊
IMMUNOLOGY
卷 141, 期 1, 页码 70-78出版社
WILEY-BLACKWELL
DOI: 10.1111/imm.12169
关键词
aggrecan; B lymphocyte; CD4(+); T lymphocyte; extracellular matrix; rheumatoid arthritis
类别
资金
- JGW Patterson Foundation
- Newcastle Healthcare Charity
- Newcastle upon Tyne Hospitals NHS Charity
- Arthritis Research UK PhD studentship
- Newcastle University
- MRC [MR/K006312/1] Funding Source: UKRI
- Medical Research Council [MR/K006312/1] Funding Source: researchfish
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.
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