Illuminating vitamin D effects on B cells – the multiple sclerosis perspective

Abstract

SummaryVitamin D is associated with many immune-mediated disorders. In multiple sclerosis (MS) a poor vitamin D status is a major environmental factor associated with disease incidence and severity. The inflammation in MS is primarily T-cell-mediated, but increasing evidence points to an important role for B cells. This has paved the way for investigating vitamin D effects on B cells. In this review we elaborate on vitamin D interactions with antibody production, T-cell-stimulating capacity and regulatory B cells. Although in vitro plasma cell generation and expression of co-stimulatory molecules are inhibited and the function of regulatory B cells is promoted, this is not supported by in vivo data. We speculate that differences might be explained by the B-cell-Epstein-Barr virus interaction in MS, the exquisite role of germinal centres in B-cell biology, and/or in vivo interactions with other hormones and vitamins that interfere with the vitamin D pathways. Further research is warranted to illuminate this tube-versus-body paradox.

Vitamin D supplementation of initially vitamin D-deficient mice diminishes lung inflammation with limited effects on pulmonary epithelial integrity

“…However, these results do not corroborate other in vitro studies, which show that 1,25(OH) 2 D downregulates CD86 on B cells during activation (reviewed in Rolf et al. ). Increased presence of IgG in the lungs with dietary vitamin D may have benefits to prevent the colonization of pathogens (through processes such as IgG‐mediated opsonization).…”

“…We observed reduced levels of IgG in the BALF of vitamin D-deficient mice, compared to mice fed a diet supplemented with vitamin D. In addition, reduced CD86 expression was observed on B cells in the ADLN of vitamin D-deficient mice, compared to mice fed a vitamin D-containing diet. However, these results do not corroborate other in vitro studies, which show that 1,25(OH) 2 D downregulates CD86 on B cells during activation (reviewed in Rolf et al 2016). Increased presence of IgG in the lungs with dietary vitamin D may have benefits to prevent the colonization of pathogens (through processes such as IgGmediated opsonization).…”

“…In vitro stimulation of B cells enriched from human blood with active 1,25(OH) 2 D has previously been shown to reduce the proportion of IgG‐secreting B cells, decreasing levels of IgG in tissue culture supernatants (Rolf et al. ). However, we observed an opposite effect with increased IgG levels in the BALF of VitD + mice compared to VitD − mice (Fig.…”

“…In addition to promoting immune tolerance through Foxp3+ regulatory T cells and tolerogenic DCs, other immune pathways are modulated by vitamin D Muehleisen and Gallo 2013). B cells are targets of vitamin D, and increase their expression of the VDR and CYP27B1 upon activation (reviewed by Rolf et al 2016). We observed reduced levels of IgG in the BALF of vitamin D-deficient mice, compared to mice fed a diet supplemented with vitamin D. In addition, reduced CD86 expression was observed on B cells in the ADLN of vitamin D-deficient mice, compared to mice fed a vitamin D-containing diet.…”

The Modulatory Effects of Vitamin D on the Expression of IL-12 and TGF-β in the Spinal Cord and Serum of Mice with Experimental Autoimmune Encephalomyelitis

“…Previous reports indicated an association between vitamin D deficiency and higher incidence and severity of MS (23)(24)(25). Furthermore, inverse correlations have been found between cerebral lesions, brain atrophy and the level of disability (26).…”