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

Abstract

Vitamin 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.

Keywords: B cells; Epstein-Barr virus; autoimmune; multiple sclerosis; plasma cells; vitamin D.

Figure 1

Schematic overview of the plasma cell generation in vitro and in vivo, with the hypothesized vitamin D effects explaining the tube‐versus‐body paradox. (a) In vitro activation of B cells in the presence of vitamin D inhibits plasma cell generation and the subsequent immunoglobulin production. No germinal centres (GCs) and survival niches (SNs) are present. (b) In vivo plasma cell generation outside the central nervous system may occur outside or (in most cases) within lymph secondary lymphoid tissue/GCs. In case GC processes (class switch recombination/somatic hypermutation) are involved, plasma blasts may be generated with a selection advantage for becoming long‐lived plasma cells. Those reside in survival niches, enabling ongoing immunoglobulin production (stable immunoglobulin levels). (c) In vivo plasma cell generation within the central nervous system probably takes place in ectopic lymphoid follicless. Here functionally inferior GCs compared with the ones of secondary lymphoid tissue, generate plasma blasts without the selection advantage for becoming long‐lived plasma cells. Abbreviations: B, B cell (naive/memory); PB, plasma blast; PC, plasma cell; CNS, central nervous system; SLT, secondary lymphoid tissue; TZ, T‐cell zone; GC, germinal centre; Bm, memory B cell; PC _sl, short‐lived plasma cell; PC _ll, long‐lived plasma cell; SN, survival niche; ELFs, ectopic lymphoid follicles