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John W. Morgan, David J. Sliney, Deborah M. Morgan, Abby L. Maizel, Differential Regulation of Gene Transcription in Subpopulations of Human B Lymphocytes by Vitamin D3
*, Endocrinology, Volume 140, Issue 1, 1 January 1999, Pages 381–391, https://doi.org/10.1210/endo.140.1.6395This work was supported in part by NIH Grant R29-DK-49649 and funds from the Department of Pathology Teaching and Research Foundation.
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Abstract
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.
