Differential regulation of gene transcription in subpopulations of human B lymphocytes by vitamin D3.
We have previously shown that freshly extirpated normal human tonsil B cells, which are phenotypically diverse, representing different stages of cellular activation and differentiation, are refractory to the effects of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and require specific activation signals for induction of responsiveness. To determine whether these diversely activated B cell populations respond to 1,25-(OH)2D3, human tonsil B cells were density fractionated and evaluated biochemically and functionally. Low density tonsil B cells, representing the centroblastic fraction, were observed to constitutively express vitamin D receptor message and protein. In contrast, high density quiescent tonsillar B cells had no detectable vitamin D receptor message or protein and required stimulation in vitro for their up-regulation. Biological responsiveness to 1,25-(OH)2D3 was assessed by messenger RNA (mRNA) expression of the vitamin D-dependent enzyme, 25-hydroxyvitamin D3 24-hydroxylase. Low density centroblastic B cells did not require exogenous surface activation for expression of 24-hydroxylase mRNA, which was detectable after 6 h of culture in the presence of 1,25-(OH)2D3. In contrast, high density tonsil B cells required in vitro activation for induction of 24-hydroxylase mRNA, and expression was not detectable for up to 48 h of culture. These observations suggest that reactivity of normal B cell populations to vitamin D is dependent upon their specific stage of activation.
Morgan
J W
JW
Department of Pathology, Roger Williams Medical Center, Boston University, Massachusetts 02118, USA. john_morgan@brown.edu
Sliney
D J
DJ
Morgan
D M
DM
Maizel
A L
AL
D000818:Animals; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D002499:Centrifugation, Density Gradient; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System; D006801:Humans; D007700:Kinetics; D051379:Mice; D014066:Palatine Tonsil / Q000166:cytology; D016133:Polymerase Chain Reaction; D051381:Rats; D013250:Steroid Hydroxylases / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D020298:U937 Cells; D065668:Vitamin D3 24-Hydroxylase
D000911:Antibodies, Monoclonal; D002762:Cholecalciferol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol