TLR9-signaling is required for turning retinoic acid into a potent stimulator of RP105 (CD180)-mediated proliferation and IgG synthesis in human memory B cells.

The role of vitamin A in the various parts of the immune system remains elusive. Toll-like receptors (TLRs) are involved in innate polyclonal activation of B-cells, and as such they are important for maintaining long-lasting first line defense against pathogens. Here we explore the impact of all-trans retinoic acid (RA) on B cell responses mediated via the TLR homolog RP105 (CD180). We show that RA slightly reduces the proliferation and IgG production in CD27+ memory B cells stimulated by anti-RP105 alone. However, co-stimulation with the TLR9-ligand CpG results in turning RA into a potent stimulator of RP105-induced proliferation and IgG synthesis in memory B cells. The results emphasize the important role of RA in stimulating TLR-mediated polyclonal activation and differentiation of B cells, and reveal the complex interplay between various TLRs that may underlie the ability of RA to fight pathogens.