1,25-Dihydroxyvitamin D-3 induces CCR10 expression in terminally differentiating human B cells

In the B cell lineage, CCR10 is known to be selectively expressed by plasma cells, especially those secreting IgA. In this study, we examined the regulation of CCR10 expression in terminally differentiating human B cells. As reported previously, IL-21 efficiently induced the differentiation of activated human CD19(+) B cells into IgD(-)CD38(+) plasma cells in vitro. A minor proportion of the resulting CD19(+)IgD(-)CD38(+) cells expressed CCR10 at low levels. 1,25-Dihydroxyvitamin D-3 (1,25-(OH)(2)D-3), the active metabolite of vitamine D-3, dramatically increased the proportion of CD19(+)IgD(-)CD38(+) cells expressing high levels of CCR10. The 1,25(OH)2D3 also increased the number of CCR10(+) cells expressing surface IgA, although the majority of CCR10(+) cells remained negative for surface IgA. Thus, 1,25-(OH)(2)D-3 alone may not be sufficient for the induction of IgA expression in terminally differentiating human B cells. To further determine whether 1,25-(OH)(2)D-3 directly induces CCR10 expression in terminally differentiating B cells, we next performed the analysis on the human CCR10 promoter. We identified a proximal Ets-1 site and an upstream potential vitamin D response element to be critical for the inducible expression of CCR10 by 1,25-(OH)(2)D-3. We confirmed the specific binding of Ets-1 and 1,25-(OH)(2)D-3-activated vitamin D receptor to the respective sites. In conclusion, 1,25-(OH)(2)D-3 efficiently induces CCR10 expression in terminally differentiating human B cells in vitro. Furthermore, the human CCR10 promoter is cooperatively activated by Ets-1 and vitamin D receptor in the presence of 1,25-(OH)(2)D-3.