Vitamin D-Mediated gene regulation in phenotypically defined human B cell subpopulations

Isolation of distinct subpopulations of density-fractionated normal human B lymphocytes reveals that the requirements for up-regulation of the vitamin D receptor (VDR) and initiation of 1 alpha,25-dihydroxyvitamin D-3 [1 alph a,25-(OH)(2)D-3]-mediated genomic trans-activation are dependent upon the s tate of cellular activation. The kinetics of the response differ widely amo ng these B cell subpopulations. However, these density-fractionated B cell subpopulations are phenotypically diverse and therefore are not representat ive of distinct stages of B cell maturation and differentiation. To examine the role of B cell differentiation on the induction and maintenance of bio logical receptivity to 1,25-(OH)(2)D-3, we purified naive, germinal center, and memory B cells based on their expression of CD38 and CD44 surface anti gens and surface Ig isotype. These phenotypically defined B cell subpopulat ions were all found to constitutively express VDR, and all exhibited simila r activation requirements and kinetics for initiation of 1,25-(OH)(2)D-3-me diated genomic trans-activation. Taken together, these results suggest that defined stages of differentiation in normal B cells are not significant pr edicators of VDR expression or receptivity to 1,25-(OH)(2)D-3. Rather, the degree of cellular activation, regardless of maturation stage, determines w hether the effects of this immunoregulatory hormone will influence a mature B lymphocyte.