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 naïve B cell responses seem to require additional, but as yet unidentified, signals. We explored the effects of RP105 (CD180) on CpG DNA-activated naïve and memory B cells from normal controls and patients with common variable immunodeficiency (CVID). RP105 dramatically enhanced CpG DNA-induced proliferation/survival by naïve B cells but not by memory B cells. This enhancement was mediated by TLR9 upregulation induced by RP105, leading to Akt activation and sustained NF-kappaB 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 interleukin-21 stimulation. Thus, RP105 strongly affects expansion of the naïve B-cell pool, and suggests that the putative RP105 ligand (s) upon cytokine stimulation facilitates antibody-mediated acute pathogen clearance.
Potentiation of TLR9 responses for human naïve B-cell growth through RP105 signaling
RP105 신호 전달을 통한 인간 미성숙 B세포 성장에 대한 TLR9 반응의 증강
[Category] 폐렴구균 감염증,
[Article Type] journal-article
[Source] pubmed
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