Potentiation of TLR9 responses for human naive B-cell growth through RP105 signaling

Toll-like receptor 9 (TLR9) signals induce important pathways in the early defense against microbial pathogens. Although TLR9 signaling can activate memory B cells directly, efficient naive B cell responses seem to require additional, but as yet unidentified, signals. We explored the effects of RP105 (CD180) on CpG DNA-activated naive and memory B cells from normal controls and patients with common variable immunodeficiency (CVID). RP105 dramatically enhanced CpG DNA-induced proliferation/survival by naive B cells but not by memory B cells. This enhancement was mediated by TLR9 upregutation induced by RP105, leading to Akt activation and sustained NF-kappa B activation. CpG DNA-activated CVID B cells showed enhancement of proliferation/survival by RP105 and produced specific IgM antibody to Streptococcus pneumoniae polysaccharides in response to interieukin-21 stimulation. Thus, RP105 strongly affects expansion of the naive B-cell pool, and suggests that the putative RP105 ligand (s) upon cytokine stimulation facilitates antibody-mediated acute pathogen clearance. (C) 2010 Elsevier Inc. All rights reserved.