Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B

Guilin Qiao; Minxiang Lei; Zhenping Li; Yonglian Sun; Andrew Minto; Yang-Xin Fu; Haiyan Ying; Richard J Quigg; Jian Zhang

doi:10.4049/jimmunol.179.7.4473

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Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B

Journal article

Peer reviewed

Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B

Guilin Qiao, Minxiang Lei, Zhenping Li, Yonglian Sun, Andrew Minto, Yang-Xin Fu, Haiyan Ying, Richard J Quigg and Jian Zhang

The Journal of immunology (1950), Vol.179(7), pp.4473-4479

10/01/2007

DOI: 10.4049/jimmunol.179.7.4473

PMID: 17878343

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Abstract

It has been documented that CD40 is essential for B cell function. Casitas-B-lineage lymphoma protein-b (Cbl-b), an adapter protein and ubiquitin ligase, has been shown to regulate the activation of T and B cells through their Ag receptors. In this study, we report that CD40-induced B cell proliferation is significantly augmented in mice lacking Cbl-b. Furthermore, Cbl-b(-/-) mice display enhanced thymus-dependent Ab responses and germinal center formation, whereas introduction of CD40 deficiency abolishes these effects. Hyper thymus-dependent humoral response in Cbl-b(-/-) mice is in part due to an intrinsic defect in B cells. Mechanistically, Cbl-b selectively down-modulates CD40-induced activation of NF-kappaB and JNK. Cbl-b associates with TNF receptor-associated factor 2 upon CD40 ligation, and inhibits the recruitment of TNF receptor-associated factor 2 to the CD40. Together, our data suggest that Cbl-b attenuates CD40-mediated NF-kappaB and JNK activation, thereby suppressing B cell responses.

Proto-Oncogene Proteins c-cbl - metabolism

Cell Proliferation

Ubiquitin - metabolism

NF-kappa B - metabolism

CD40 Ligand - immunology

Lymphocyte Activation - immunology

CD40 Antigens - metabolism

CD40 Ligand - metabolism

Proto-Oncogene Proteins c-cbl - deficiency

Proto-Oncogene Proteins c-akt - metabolism

B-Lymphocytes - metabolism

Proto-Oncogene Proteins c-cbl - genetics

B-Lymphocytes - cytology

Down-Regulation

Cells, Cultured

TNF Receptor-Associated Factor 2 - metabolism

Mice, Knockout

Animals

B-Lymphocytes - immunology

Adaptor Proteins, Signal Transducing - deficiency

Adaptor Proteins, Signal Transducing - genetics

Protein Binding

Mice

Mice, Inbred BALB C

Adaptor Proteins, Signal Transducing - metabolism

CD40 Antigens - immunology

Mitogen-Activated Protein Kinases - metabolism

Details

Title: Subtitle: Negative regulation of CD40-mediated B cell responses by E3 ubiquitin ligase Casitas-B-lineage lymphoma protein-B
Creators: Guilin Qiao - Section of Nephrology, Department of Medicine, University of Chicago, Chicago, IL 6063, USA
Minxiang Lei
Zhenping Li
Yonglian Sun
Andrew Minto
Yang-Xin Fu
Haiyan Ying
Richard J Quigg
Jian Zhang
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.179(7), pp.4473-4479
DOI: 10.4049/jimmunol.179.7.4473
PMID: 17878343
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: K02 AR049047 / NIAMS NIH HHS R01AR049775 / NIAMS NIH HHS
Language: English
Date published: 10/01/2007
Academic Unit: Pathology
Record Identifier: 9984047629302771

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