IL-10 production in B cells is confined to CD154+ cells in patients with systemic lupus erythematosus

Characterization of a rare IL-10–competent B-cell subset in humans that parallels mouse regulatory B10 cells

“…Consistent with this, IL-10 production by blood B cells is reported to be higher in patients with rheumatoid arthritis, lupus, and systemic sclerosis. 23,24,26 Moreover, elevated B10/B10pro-cell frequencies in humans parallel what has been found during inflammation 12,13 and autoimmunity in mice. 14,21 Although patient cohorts with recent-onset disease and clinically active disease across multiple organ systems will be needed to fully assess the relationship of blood B10-cell numbers with clinical, laboratory, and treatment status, none of the patients or patient groups had significantly lower blood B10-cell numbers than age-matched healthy controls.…”

“…Previous studies of IL-10 production by human B cells have predominantly studied bulk B-cell populations using stimulation and assay conditions that were not optimized for quantifying or characterizing individual B cells that were competent to express IL-10. 25,26,[39][40][41][42][43] Nonetheless, the results herein demonstrate that rare B10 and B10pro cells that are competent to express IL-10 exist in human blood and can be quantified in vitro.…”

“…Studies of B-cell IL-10 production in humans have yielded diverse results that are currently difficult to unify into a coherent model. [23][24][25][26][27][28] It is also unknown whether human B10 cells share overlapping physiologic triggers with mouse B10 cells that lead to IL-10 production and their expansion in vitro. 12,13,21 Therefore, the purpose of the current study was to enumerate and characterize the IL-10 competent B10 and B10pro cell subsets in humans.…”

Interleukin 21–Induced Granzyme B–Expressing B Cells Infiltrate Tumors and Regulate T Cells

“…In the present study, we identified IL-21 as key cytokine for the induction of human Bregs. Their phenotype includes surface markers such as CD1d, CD38, IgM, CD10, CD86, and CD154 (5,6,8,9,35) but also molecules with actual regulatory functions including GrB (17)(18)(19)(20), IL-10 (2, 5, 6), IDO (36), and CD25 (37,38). IL-21 is known to have a variety of effects on B cells, depending on their maturation stage and the presence of further costimulatory signals.…”

“…1), a capacity they seem to share with Tregs (17)(18)(19) and regulatory dendritic cells (20). To define in more detail the phenotype of IL-21-induced GrB þ B cells, we tested a variety of surface antigens described in the past to characterize Breg (5,6,8,9,35). These antigens include activation markers, molecules of the immunoglobulin superfamily, costimulatory molecules, enzymes, and adhesion molecules.…”