TY - JOUR
T1 - B cell lymphoma 10 is essential for FcεR-mediated degranulation and IL-6 production in mast cells
AU - Chen, Yuhong
AU - Pappu, Bhanu P.
AU - Zeng, Hu
AU - Xue, Liquan
AU - Morris, Stephan W.
AU - Lin, Xin
AU - Wen, Renren
AU - Wang, Demin
PY - 2007/1/1
Y1 - 2007/1/1
N2 - The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the functions of the AgRs in T and B cells. In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of FceR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcεR-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient mast cells have normal FcεR-mediated Ca2+ flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcεR-mediated activation of NF-κB and decreased activation of AP-1. Thus, Bcl10 is essential for FcεR-induced activation of AP-1, NF-κB, degranulation, and cytokine production in mast cells.
AB - The adaptor protein B cell lymphoma 10 (Bcl10) plays an essential role in the functions of the AgRs in T and B cells. In this study, we report that Bcl10 also plays an important role in mast cells. Bcl10 is expressed in mast cells. Although Bcl10-deficient mast cells undergo normal development, we demonstrate that Bcl10 is essential for specific functions of FceR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcεR-mediated degranulation, indicated by decreased serotonin release, and impaired cytokine production, measured by release of IL-6. In addition, Bcl10-deficient mice display impaired IgE-mediated passive cutaneous anaphylaxis. Moreover, although Bcl10-deficient mast cells have normal FcεR-mediated Ca2+ flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcεR-mediated activation of NF-κB and decreased activation of AP-1. Thus, Bcl10 is essential for FcεR-induced activation of AP-1, NF-κB, degranulation, and cytokine production in mast cells.
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U2 - 10.4049/jimmunol.178.1.49
DO - 10.4049/jimmunol.178.1.49
M3 - Article
C2 - 17182539
AN - SCOPUS:33845917204
SN - 0022-1767
VL - 178
SP - 49
EP - 57
JO - Journal of Immunology
JF - Journal of Immunology
IS - 1
ER -