Regulatory B cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γproduction

• Regulatory B (Breg) cells can dampen inflammation, autoreactivity, and transplant rejection. We investigated the frequencies, phenotypes, and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge as to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24hiCD27+ and CD24hiCD38hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in vitro and levels in plasma were determined with enzyme-linked immunosorbent assay. Frequencies of CD24hiCD27+ B-cells were reduced both during active disease and remission compared with HC (P = 0.005 and P = 0.010, respectively), whereas CD24hiCD38hi B-cells did not differ. Patient CD24hiCD27+ B-cells exhibited decreased expression of CD25 but increased expression of PD-L1 and PD-L2 during remission. B-cells from GPA patients regulated T-cell proliferation but failed to regulate interferon (IFN)-γproduction (median T-cells alone 222 ng/ml vs. T-cells + B-cells 207 ng/ml, P = 0.426). IFN-γwas also elevated in patient plasma samples (P = 0.016). In conclusion, GPA patients exhibit altered numbers and phenotypes of CD24hiCD27+ B-cells. This is accompanied by a disability to control T-cell production of Th1-type cytokines during remission, which might be of fundamental importance for the granulomatous inflammation that characterizes the chronic phase of this disease. © 2023 The Author(s). Published by Oxford University Press on behalf of the British Society for Immunology.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

B-Lymphocytes

Regulatory; Cytokines; Granulomatosis with Polyangiitis; Humans; Inflammation; Interferon-gamma; azathioprine; CD24 antigen; CD27 antigen; chemokine; cyclophosphamide; cytokine; gamma interferon; interleukin 2 receptor; interleukin 2 receptor alpha; methotrexate; mycophenolate mofetil; myeloperoxidase; prednisolone; programmed death 1 ligand 1; rituximab; cytokine; gamma interferon; adult; aged; Article; autoimmunity; B lymphocyte; B lymphocyte subpopulation; cell function; cell population; cell proliferation; clinical article; coculture; comparative study; controlled study; cytokine production; disease activity; enzyme linked immunosorbent assay; female; flow cytometry; follow up; gene expression; gene frequency; human; human cell; immunoregulation; in vitro study; male; middle aged; peripheral blood mononuclear cell; phenotype; proliferation index; protein expression; regulatory B lymphocyte; regulatory mechanism; remission; T lymphocyte; T lymphocyte activation; treatment failure; vasculitis; Wegener granulomatosis; inflammation; metabolism

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