Low Levels of Vitamin D Promote Memory B Cells in Lupus

Abstract

<i>Background</i>: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The <i>Act1-/-</i> mouse is a spontaneous model of lupus and Sjögren's syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the <i>Act1-/-</i> mouse. <i>Methods</i>: <i>Act1-/-</i> mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. <i>Results</i>: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. <i>Conclusion</i>: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients.