Antigen-specific B cell response regulation by IL-10– producing tolerogenic dendritic cells

B cells regulate immune responses via antibody production and antigen (Ag) presentation. Although B cell depletion is used therapeutically, it may be associated with side effects, highlighting the need for alternative B cell–targeted approaches. While tolerogenic dendritic cells (tolDC) are known to modulate T cell responses, their impact on B cells is poorly defined. We show that IL-10– producing tolDC (DC^IL-10) regulate B cell responses through direct and indirect mechanisms. DC^IL-10 enhances T cell–independent human B cell proliferation and differentiation while suppressing Ag-specific memory B cells via T cell inhibition in vitro and dampen Ag-specific IgG production in preclinical humanized and murine models. These findings reveal a dual mechanism by which DC^IL-10 regulates B cell responses, broadening their application as a cell-based approach to treating immune-mediated diseases by targeting both B and T cells.