Impaired T cell activation and cytokine production by calcitriol‐primed human B cells

Summary The biologically active form of vitamin D 3 , 1, 25‐dihydroxyvitamin D 3 (calcitriol), is a potent modulator of the immune response. We have shown previously that calcitriol modulates the immunoglobulin response in vitro and in vivo in mice and humans. To analyse the underlying molecular mechanisms we studied whether calcitriol‐primed B cells modulate T cell activation and function. Human B cells were stimulated with anti‐ CD 40 and interleukin ( IL )‐4 in the presence of increasing concentrations of calcitriol. After removal of calcitriol, primed B cells were co‐cultured with autologous CD 4 + T cells; the B cell phenotype T cell activation and their consecutive cytokine production were also assessed. Naive T cells co‐cultured with calcitriol‐primed naive B cells showed a reduced expansion, nuclear factor of activated T cells, cytoplasmic 2 ( NFAT c2) expression and cytokine production upon restimulation. CD 86 expression on B cells after calcitriol priming was identified as an underlying mechanism, as T cell activation and expansion was rescued by activating anti‐ CD 28 antibodies. Our data indicate that calcitriol‐primed B cells display an impaired capacity to activate T cells. Taken together, we identified a novel B cell‐dependent vitamin D immune regulatory mechanism, namely by decreased co‐stimulation of calcitriol‐primed B cells.