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Differential Regulation of Gene Transcription in Subpopulations of Human B Lymphocytes by Vitamin D₃¹

Section of Experimental Pathology, Department of Pathology, Roger Williams Medical Center, Boston University, Boston, Massachusetts 02118; and Brown University, Providence, Rhode Island 02908

Address all correspondence and requests for reprints to: Dr. John W. Morgan, Department of Pathology, Roger Williams Medical Center, Providence, Rhode Island 02908. E-mail: john_morgan{at}brown.edu

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.

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				J. W. Morgan, N. Kouttab, D. Ford, and A. L. Maizel Vitamin D-Mediated Gene Regulation in Phenotypically Defined Human B Cell Subpopulations Endocrinology, September 1, 2000; 141(9): 3225 - 3234. [Abstract] [Full Text] [PDF]