1,25-Dihydroxyvitamin D3-mediated inhibition of human B cell differentiation

We have examined the mechanisms of 1,25-dihydroxyvitamin D3 (D3)-mediated inhibition of human B cell differentiation to immunoglobulin (Ig) secreting cells. B lymphocytes were purified from human tonsils and peripheral blood mononuclear cells. Mononuclear cells were separated into adherent cells and nonadherent cells. Cells were stimulated with Staphylococcus aureus Cowen I (SAC) or pokeweed mitogen (PWM) for 7 days and immunoglobulin production was measured by ELISA assay, 1,25-dihydroxyvitamin D3 was added at different times during cultures. 1,25-Dihydroxyvitamin D3, in a dose-dependent manner, inhibited both SAC and PWM-induced Ig production by mononuclear cells. The maximum inhibition was observed when 1,25-dihydroxyvitamin D3 was added at the beginning of culture, but inhibition could still be observed when 1,25-dihydroxyvitamin D3 was added on day 4 of cultures. The inhibitory effect of 1,25-dihydroxyvitamin D3 on Ig production was significantly greater on mononuclear cells than on nonadherent cells. Addition of in vitro purified IL-1 to nonadherent cells enhanced 1,25-dihydroxyvitamin D3-induced inhibition of Ig production. 1,25-Dihydroxyvitamin D3 also inhibited the expression of IL-2 receptors on B cells activated with SAC. 1,25-dihydroxyvitamin D3 did not inhibit Ig production by SAC preactivated B cell blasts in response to T cell supernatants. These data suggest that vitamin D3 inhibits Ig production by inhibiting IL-2 receptor expression on B cells and via its effect on adherent macrophages. Vitamin D3 does not influence the effect of differentiation factors on activated B cells that have already expressed growth/differentiation factor receptors.