4.0 Article

Increased numbers of CD5+ B lymphocytes with a regulatory phenotype in spondylarthritis

Journal

ARTHRITIS AND RHEUMATISM
Volume 64, Issue 6, Pages 1859-1868

Publisher

WILEY-BLACKWELL
DOI: 10.1002/art.34364

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Funding

  1. Netherlands Organization for Scientific Research
  2. Dutch Arthritis Foundation (Reumafonds)

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Objective Whether and how B lymphocytes contribute to the pathogenesis of spondylarthritis (SpA), a seronegative arthritis associated with gut inflammation, remains unknown. Because innate-like CD5+ B lymphocytes with regulatory functions have been identified in colitis models, we undertook the present study to analyze the presence and function of CD5+ B cells in human SpA. Methods Peripheral blood B cells from patients with SpA, patients with rheumatoid arthritis (RA), and healthy controls were analyzed by flow cytometry. Synovial biopsy samples were evaluated by immunohistochemistry analysis. Sorted CD5+ and CD5- B cells were analyzed for somatic hypermutation, expression of costimulatory molecules, and cytokine production. Results The naive, marginal zonelike, and to a lesser extent memory B cell compartments in patients with SpA exhibited a clear and specific increase of CD5+ B cells, which was not found in patients with RA. This increase was not due to either B cell activation or preferential migration of CD5- B cells to the inflamed synovium. Consistent with their phenotype and the low-affinity polyreactive immunoglobulins produced by their murine counterpart cells, CD5+ B cells from patients with SpA showed low levels of somatic hypermutation. With regard to antigen presentation, CD5+ B cells expressed slightly increased HLADR levels but low CD80 and CD86 levels. In vitro activation failed to up-regulate these costimulatory molecules but induced significant production of interleukin-10 and interleukin-6 by CD5+ B cells. Conclusion CD5+ B cells are specifically increased in SpA. Analysis of somatic hypermutation, expression of antigen-presenting and costimulatory molecules, and cytokine production indicates that this B cell subset has regulatory capacities. Further investigation of the potential role of CD5+ cells in SpA is warranted.

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