title: Defective Function of CD24(+)CD38(+) Regulatory B Cells in Ankylosing Spondylitis.
abstract: 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.
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Meng
authors.initials: M
authors.lastname: Chen
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Ren
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Kaining
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 2 BGC Biotechnology Research Center , Jinan, China .
authors.forename: Yuan
authors.initials: Y
authors.lastname: Fang
authors.affiliation: 2 BGC Biotechnology Research Center , Jinan, China .
authors.forename: Xiaozhou
authors.initials: X
authors.lastname: Yan
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Dayong
authors.initials: D
authors.lastname: Peng
authors.affiliation: 3 Department of Orthopedics, The Second Hospital of Shandong University , Jinan, China .
authors.forename: Chunzheng
authors.initials: C
authors.lastname: Gao
authors.affiliation: 1 Department of Orthopedics, Shandong Qianfoshan Hospital, Shandong University , Jinan, China .
authors.forename: Shufeng
authors.initials: S
authors.lastname: Li
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000276:immunology* / Q000473:pathology
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; C508609:IL10 protein, human; D008562:Membrane Glycoproteins; D016753:Interleukin-10; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1