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
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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
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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 |
|