RRC ID 43099
著者 Shinners NP, Carlesso G, Castro I, Hoek KL, Corn RA, Woodland RT, Scott ML, Wang D, Khan WN.
タイトル Bruton's tyrosine kinase mediates NF-kappa B activation and B cell survival by B cell-activating factor receptor of the TNF-R family.
ジャーナル J Immunol
Abstract Loss of Bruton's tyrosine kinase (Btk) function results in mouse Xid disease characterized by a reduction in mature B cells and impaired humoral immune responses. These defects have been mainly attributed to impaired BCR signaling including reduced activation of the classical NF-kappaB pathway. In this study we show that Btk also couples the receptor for B cell-activating factor (BAFF) of the TNF family (BAFF-R) to the NF-kappaB pathway. Loss of Btk results in defective BAFF-mediated activation of both classical and alternative NF-kappaB pathways. Btk appears to regulate directly the classical pathway in response to BAFF such that Btk-deficient B cells exhibit reduced kinase activity of IkappaB kinase gamma-containing complexes and defective IkappaBalpha degradation. In addition, Btk-deficient B cells produce reduced levels of NF-kappaB2 (p100) basally and in response to stimulation via the BCR or BAFF-R, resulting in impaired activation of the alternative NF-kappaB pathway by BAFF. These results suggest that Btk regulates B cell survival by directly regulating the classical NF-kappaB pathway under both BCR and BAFF-R, as well as by inducing the expression of the components of alternative pathway for sustained NF-kappaB activation in response BAFF. Thus, impaired BCR- and BAFF-induced signaling to NF-kappaB may contribute to the observed defects in B cell survival and humoral immune responses in Btk-deficient mice.
巻・号 179(6)
ページ 3872-80
公開日 2007-9-15
DOI 10.4049/jimmunol.179.6.3872
PII 179/6/3872
PMID 17785824
MeSH Agammaglobulinaemia Tyrosine Kinase Animals B-Cell Activation Factor Receptor / deficiency B-Cell Activation Factor Receptor / genetics B-Cell Activation Factor Receptor / physiology B-Lymphocytes / enzymology* B-Lymphocytes / immunology B-Lymphocytes / metabolism B-Lymphocytes / pathology Cell Survival / genetics Cell Survival / immunology Cells, Cultured Mice Mice, Inbred C57BL Mice, Knockout Mice, Mutant Strains NF-kappa B / metabolism* Protein-Tyrosine Kinases / deficiency Protein-Tyrosine Kinases / genetics Protein-Tyrosine Kinases / physiology* Receptors, Antigen, B-Cell / physiology Signal Transduction / genetics Signal Transduction / immunology
IF 4.886
引用数 71
WOS 分野 IMMUNOLOGY
リソース情報
ヒト・動物細胞