Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation.

Abstract

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) can modulate immune responses, but whether it directly affects B cell function is unknown. Patients with systemic lupus erythematosus, especially those with antinuclear Abs and increased disease activity, had decreased 1,25(OH)(2)D(3) levels, suggesting that vitamin D might play a role in regulating autoantibody production. To address this, we examined the effects of 1,25(OH)(2)D(3) on B cell responses and found that it inhibited the ongoing proliferation of activated B cells and induced their apoptosis, whereas initial cell division was unimpeded. The generation of plasma cells and postswitch memory B cells was significantly inhibited by 1,25(OH)(2)D(3), although the up-regulation of genetic programs involved in B cell differentiation was only modestly affected. B cells expressed mRNAs for proteins involved in vitamin D activity, including 1 alpha-hydroxylase, 24-hydroxylase, and the vitamin D receptor, each of which was regulated by 1,25(OH)(2)D(3) and/or activation. Importantly, 1,25(OH)(2)D(3) up-regulated the expression of p27, but not of p18 and p21, which may be important in regulating the proliferation of activated B cells and their subsequent differentiation. These results indicate that 1,25(OH)(2)D(3) may play an important role in the maintenance of B cell homeostasis and that the correction of vitamin D deficiency may be useful in the treatment of B cell-mediated autoimmune disorders.

• Authors: Sheng Chen, Gary P Sims, Xiao Xiang Chen, Yue Ying Gu, Shunle Chen, Peter E Lipsky
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 179 Issue 3 Pg. 1634-47 (Aug 01 2007) ISSN: 0022-1767 [Print] United States
• PMID: 17641030 (Publication Type: Journal Article)

Chemical References

• Growth Inhibitors
• Immunologic Factors
• Receptors, Calcitriol
• Vitamin D
• 25-hydroxyvitamin D
• Steroid Hydroxylases
• Vitamin D3 24-Hydroxylase
• ADP-ribosyl Cyclase 1
• Calcitriol

Topics

• ADP-ribosyl Cyclase 1 (biosynthesis)
• Adolescent
• Adult
• Aged
• Apoptosis (drug effects, genetics, immunology)
• B-Lymphocytes (cytology, drug effects, enzymology, immunology)
• Calcitriol (deficiency, pharmacology, physiology)
• Cell Differentiation (drug effects, genetics, immunology)
• Cells, Cultured
• Down-Regulation (drug effects, genetics, immunology)
• Female
• Gene Expression Regulation (drug effects)
• Growth Inhibitors (genetics, physiology)
• Humans
• Immunologic Factors (deficiency, pharmacology, physiology)
• Lupus Erythematosus, Systemic (drug therapy, immunology, pathology)
• Lymphocyte Activation (drug effects)
• Male
• Middle Aged
• Plasma Cells (drug effects, pathology)
• Receptors, Calcitriol (biosynthesis, genetics)
• Steroid Hydroxylases (biosynthesis, genetics)
• Vitamin D (analogs & derivatives, antagonists & inhibitors, blood)
• Vitamin D3 24-Hydroxylase