Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease strongly associated with HLA-B*27, an major histocompatibility complex (MHC) molecule that presents peptide antigen to T cells. Previously, regulatory B cells were found to suppress T cell-mediated autoimmunity induction and chronic inflammation, partially through interleukin (IL)-10 production. Here, we examined the role of regulatory B cells in AS pathogenesis. Apheresis samples from HLA-B*27-positive AS patients and non-AS healthy controls were collected. We found that although AS patients and non-AS controls presented similar frequencies of CD24+CD38+ B cells, compared to non-AS controls, those from AS patients produced less IL-10 under ex vivo condition and after CD40 and B-cell receptor (BCR) stimulation. Purified T cell-B cell cocultures showed that compared to non-AS controls, CD24+CD38+ B cells from AS patients were defective at suppressing naive and memory CD8+ T cell activation. The suppression of memory CD8+ T cells in non-AS controls appeared to be mediated by IL-10, since the addition of IL-10 mAb suppressed CD24+CD38+ B cell-mediated downregulation of proinflammatory cytokine production and proliferation. To rescue the defect in AS patients, CD24+CD38+ B cells were pretreated by CD40 and BCR stimulation, which enhanced CD24+CD38+ B cell-mediated memory CD8+ T cell suppression. Together, our data discovered a regulatory B cell defect in AS patients.
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