Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation.
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.
Chen
Sheng
S
Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Sims
Gary P
GP
Chen
Xiao Xiang
XX
Gu
Yue Ying
YY
Chen
Shunle
S
Lipsky
Peter E
PE
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D002117:Calcitriol / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D006801:Humans; D007155:Immunologic Factors / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000187:drug effects / Q000473:pathology; D018167:Receptors, Calcitriol / Q000096:biosynthesis / Q000235:genetics; D013250:Steroid Hydroxylases / Q000096:biosynthesis / Q000235:genetics; D014807:Vitamin D / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000097:blood; D065668:Vitamin D3 24-Hydroxylase
D006131:Growth Inhibitors; D007155:Immunologic Factors; D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D051997:ADP-ribosyl Cyclase 1; D002117:Calcitriol