B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells.
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 FcepsilonR. Although Bcl10-deficient mast cells have normal de novo synthesis and release of the lipid mediator arachidonic acid, the mutant cells possess impaired FcepsilonR-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 FcepsilonR-mediated Ca(2+) flux, activation of PI3K, and activation of the three types of MAPKs (ERKs, JNK, and p38), the mutant cells have markedly diminished FcepsilonR-mediated activation of NF-kappaB and decreased activation of AP-1. Thus, Bcl10 is essential for FcepsilonR-induced activation of AP-1, NF-kappaB, degranulation, and cytokine production in mast cells.
Chen
Yuhong
Y
Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
Pappu
Bhanu P
BP
Zeng
Hu
H
Xue
Liquan
L
Morris
Stephan W
SW
Lin
Xin
X
Wen
Renren
R
Wang
Demin
D
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000235:genetics; D016207:Cytokines / Q000378:metabolism*; D007073:Immunoglobulin E / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017455:Receptors, IgE / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D000097782:NF-kappaB-Inducing Kinase
D048868:Adaptor Proteins, Signal Transducing; D016718:Arachidonic Acid; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002118:Calcium; D016207:Cytokines; D007073:Immunoglobulin E; D015850:Interleukin-6; D020929:Mitogen-Activated Protein Kinase Kinases; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D017455:Receptors, IgE; D012701:Serotonin; D018808:Transcription Factor AP-1; D000097782:NF-kappaB-Inducing Kinase; C488088:Bcl10 protein, mouse