Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan.
Clin Immunol. 2010 Apr;135(1):125-36. doi: 10.1016/j.clim.2009.12.013. Epub 2010 Feb 4.
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.
Toll 样受体 9（TLR9）信号诱导微生物病原体早期防御的重要途径。虽然 TLR9 信号可以直接激活记忆 B 细胞，但有效的初始 B 细胞反应似乎需要额外的、但尚未确定的信号。我们研究了 RP105（CD180）对来自正常对照和常见可变免疫缺陷（CVID）患者的 CpG DNA 激活的初始和记忆 B 细胞的影响。RP105 显著增强了初始 B 细胞而非记忆 B 细胞对 CpG DNA 的增殖/存活反应。这种增强是由 RP105 诱导的 TLR9 上调介导的，导致 Akt 激活和持续的 NF-κB 激活。CpG DNA 激活的 CVID B 细胞通过 RP105 增强了增殖/存活，并在白细胞介素-21 刺激下产生针对肺炎链球菌多糖的特异性 IgM 抗体。因此，RP105 强烈影响初始 B 细胞池的扩增，并表明在细胞因子刺激下，假定的 RP105 配体（s）有助于抗体介导的急性病原体清除。
