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 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3]-mediated genomic trans-activation are dependent upon the state of cellular activation. The kinetics of the response differ widely among these B cell subpopulations. However, these density-fractionated B cell subpopulations are phenotypically diverse and therefore are not representative of distinct stages of B cell maturation and differentiation. To examine the role of B cell differentiation on the induction and maintenance of biological receptivity to 1,25-(OH)2D3, we purified naive, germinal center, and memory B cells based on their expression of CD38 and CD44 surface antigens and surface Ig isotype. These phenotypically defined B cell subpopulations were all found to constitutively express VDR, and all exhibited similar activation requirements and kinetics for initiation of 1,25(OH)2D3-mediated genomic trans-activation. Taken together, these results suggest that defined stages of differentiation in normal B cells are not significant predicators of VDR expression or receptivity to 1,25-(OH)2D3. Rather, the degree of cellular activation, regardless of maturation stage, determines whether the effects of this immunoregulatory hormone will influence a mature B lymphocyte.
Morgan
J W
JW
Department of Pathology, Roger Williams Hospital, Providence, Rhode Island 02908, USA. john_morgan@brown.edu
Kouttab
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Ford
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Maizel
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D001402:B-Lymphocytes / Q000502:physiology*; D002117:Calcitriol / Q000235:genetics; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics*; D018858:Germinal Center / Q000502:physiology; D006801:Humans; D014066:Palatine Tonsil / Q000166:cytology; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014807:Vitamin D / Q000235:genetics*
D012333:RNA, Messenger; D014807:Vitamin D; D002117:Calcitriol