New insights into the pathogenesis of IgA nephropathy: do toll like receptor 9-B cell activation factor-IgA class switching recombination signaling axis induce IgA hyper-production?

Renal Failure ◽  
2014 ◽  
Vol 36 (6) ◽  
pp. 970-973 ◽  
Author(s):  
Yuyuan Liu ◽  
Hong Liu ◽  
Youming Peng ◽  
Fuyou Liu
2009 ◽  
Vol 41 (3) ◽  
pp. 208 ◽  
Author(s):  
Yu-Hee Kim ◽  
Bong-Hyuk Choi ◽  
Hyae-Gyeong Cheon ◽  
Myoung-Sool Do

2011 ◽  
Vol 128 (3) ◽  
pp. 601-609.e4 ◽  
Author(s):  
Esra Ozcan ◽  
Ingrid Rauter ◽  
Lilit Garibyan ◽  
Stacey R. Dillon ◽  
Raif S. Geha

2007 ◽  
Vol 81 (18) ◽  
pp. 9748-9758 ◽  
Author(s):  
Heather J. Martin ◽  
Jae Myun Lee ◽  
Dermot Walls ◽  
S. Diane Hayward

ABSTRACT Epstein-Barr virus (EBV) infection of primary B cells causes B-cell activation and proliferation. Activation of B cells requires binding of antigen to the B-cell receptor and a survival signal from ligand-bound CD40, signals that are provided by the EBV LMP1 and LMP2A latency proteins. Recently, Toll-like receptor (TLR) signaling has been reported to provide a third B-cell activation stimulus. The interaction between the EBV and TLR pathways was therefore investigated. Both UV-inactivated and untreated EBV upregulated the expression of TLR7 and downregulated the expression of TLR9 in naive B cells. UV-inactivated virus transiently stimulated naive B-cell proliferation in the presence of the TLR7 ligand R837, while addition of the TLR7 antagonist IRS 661 impaired cell growth induced by untreated EBV. Interferon regulatory factor 5 (IRF-5) is a downstream mediator of TLR7 signaling. IRF-5 was induced following EBV infection, and IRF-5 was expressed in B-cell lines with type III latency. Expression of IRF-5 in this setting is surprising since IRF-5 has tumor suppressor and antiviral properties. B-cell proliferation assays provided evidence that EBV modulates TLR7 signaling responses. Examination of IRF-5 transcripts identified a novel splice variant, V12, that was induced by EBV infection, was constitutively nuclear, and acted as a dominant negative form in IRF-5 reporter assays. IRF-4 negatively regulates IRF-5 activation, and IRF-4 was also present in type III latently infected cells. EBV therefore initially uses TLR7 signaling to enhance B-cell proliferation and subsequently modifies the pathway to regulate IRF-5 activity.


2000 ◽  
Vol 192 (1) ◽  
pp. 23-30 ◽  
Author(s):  
Hirotaka Ogata ◽  
I-hsin Su ◽  
Kensuke Miyake ◽  
Yoshinori Nagai ◽  
Sachiko Akashi ◽  
...  

The susceptibility to infections induced by Gram-negative bacteria is largely determined by innate immune responses to bacteria cell wall lipopolysaccharide (LPS). The stimulation of B cells by LPS enhances their antigen-presenting capacity and is accompanied by B cell proliferation and secretion of large quantities of LPS-neutralizing antibodies. Similar to macrophages and neutrophils, the LPS-induced activation of B cells is dependent on Toll-like receptor (TLR)4. Here, we demonstrate that the responses of B cells to LPS are also regulated by another TLR protein, RP105, which is predominantly expressed on mature B cells in mice and humans. The analysis of mice homozygous for the null mutation in the RP105 gene revealed impaired proliferative and humoral immune responses of RP105-deficient B cells to LPS. Using originally LPS-unresponsive Ba/F3 cells expressing exogenous TLR4 and RP105, we demonstrate the functional cooperation between TLR4 and RP105 in LPS-induced nuclear factor κB activation. These data suggest the existence of the TLR4–RP105 signaling module in the LPS-induced B cell activation.


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