Potentiation of TLR9 responses for human naïve 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 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.
Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Asahi 3-1-1, Matsumoto 390-8621, Japan. yama_k@shinshu-u.ac.jp
Kazuko
K
Yamazaki
Takashi
T
Yamazaki
Shinsuke
S
Taki
Kensuke
K
Miyake
Takuma
T
Hayashi
Hans D
HD
Ochs
Kazunaga
K
Agematsu
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D048708:Cell Growth Processes / Q000276:immunology; D017074:Common Variable Immunodeficiency / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D015703:Antigens, CD; C092722:CD180 protein, human; D007075:Immunoglobulin M; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9