B cell lymphoma 10 is essential for FcepsilonR-mediated degranulation and IL-6 production in mast cells. J Immunol 2007 Jan 01;178(1):49-57
Date
12/22/2006Pubmed ID
17182539DOI
10.4049/jimmunol.178.1.49Scopus ID
2-s2.0-33845917204 (requires institutional sign-in at Scopus site) 22 CitationsAbstract
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.
Author List
Chen Y, Pappu BP, Zeng H, Xue L, Morris SW, Lin X, Wen R, Wang DAuthors
Demin Wang PhD Professor in the Microbiology and Immunology department at Medical College of WisconsinRenren Wen PhD Adjunct Associate Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAnaphylaxis
Animals
Arachidonic Acid
B-Cell CLL-Lymphoma 10 Protein
Calcium
Cell Degranulation
Cytokines
Immunoglobulin E
Interleukin-6
Mast Cells
Mice
Mice, Mutant Strains
Mitogen-Activated Protein Kinase Kinases
Phosphatidylinositol 3-Kinases
Protein Kinase C
Receptors, IgE
Serotonin
Transcription Factor AP-1
