Hypovitaminosis D upscales B-cell immunoreactivity in multiple sclerosis

J Neuroimmunol. 2016 May 15;294:18-26. doi: 10.1016/j.jneuroim.2016.03.011. Epub 2016 Mar 23.


Background: While vitamin D is increasingly recognized as a potential immune regulator of MS disease activity, its impact on B lymphocytes, however, remains ill-defined.

Methods: We assessed the impact of vitamin D on B-cell proliferation and cytokine secretion ex vivo and screened for effects of hypovitaminosis D and vitamin D supplementation on the compartmentalized distribution of B-cell subtypes in peripheral blood and cerebrospinal fluid (CSF) from patients with relapsing remitting MS (n=95) and various neurologic and healthy controls (n=57).

Results: B cells from MS patients with 25(OH)D serum levels <20ng/ml, displayed enhanced immunoreactivity ex vivo as a consequence of more vigorous responses of CD27(+) memory phenotypes. Immune responses decreased when B cells from either source were co-cultured in the presence of vitamin D or when retesting B cells from MS patients after prolonged supplementation with vitamin D. Hypovitaminosis D was detectable in the serum of 40/95 MS patients, correlated with decreased vitamin D concentrations in CSF and with higher disease activity, and was paralleled by intrathecal accumulation of CD27(+) B-cell subtypes and plasma cells.

Conclusion: B-cell immunoreactivity is attenuated by vitamin D. Our finding that vitamin D deficiency affects the intrathecal compartment and coincides with increased frequencies of effector B-cell subtypes in the CSF suggests that hypovitaminosis D might contribute to augmenting disease activity in the target organ and supports a potential benefit of vitamin D supplementation in MS.

Keywords: B lymphocytes; B-cell immunoreactivity; Cerebrospinal fluid; Hypovitaminosis D; Multiple sclerosis; Vitamin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology*
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / drug effects
  • Male
  • Middle Aged
  • Multiple Sclerosis / blood
  • Multiple Sclerosis / cerebrospinal fluid
  • Multiple Sclerosis / complications
  • Multiple Sclerosis / pathology
  • Vitamin D / pharmacology*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / cerebrospinal fluid
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / pathology
  • Vitamins / pharmacology*
  • Young Adult


  • Cytokines
  • Vitamins
  • Vitamin D