Vitamin A and vitamin D induced nuclear hormone receptor activation and its impact on B cell differentiation and immunoglobulin production.

Vitamin A and vitamin D metabolites are ligands to nuclear receptors - namely RAR, RXR and VDR. The activation of these receptors in human B cells impacts B cell maturation and function. In this review, we discuss how 9-cis retinoic acid (9cRA) and 1,25-dihydroxyvitamin D3 (calcitriol) individually or in conjunction, signal through their nuclear receptors and thereby impact B cell differentiation, immunoglobulin class switching to IgA at the expense of IgE, and also B cell migration and homing. Impact of the vitamin metabolites individually on B cell survival factors are well elucidated, be it the regulation of BAFF and APRIL, the induction of TGF-β or suppression of NF-κB. Very little is known about the impact of 9cRA and calcitriol together on B cells. Recently our group revealed that 9cRA and calcitriol together in the context of the B cell differentiation, induces naïve B cell differentiation into IgA+ plasmablasts, the functional and underlying molecular regulations however require further investigation. In conclusion, the conjunctional impact of these nuclear receptor ligands on B cell functionality is important to better understand B cell dependent clinical outcomes in allergy and autoimmunity. Within this review, we hypothesize that a balance between both vitamins is of utmost importance to provide a robust humoral immune response and a better treatment of disorders characterised by dysregulated immune responses such as IgE-dependent allergy or autoimmunity such as lupus erythematosus.