Cutting edge: molecular mechanisms of synergy between CD40 and the B cell antigen receptor: role for TNF receptor-associated factor 2 in receptor interaction

Sokol A Haxhinasto; Bruce S Hostager; Gail A Bishop

doi:10.4049/jimmunol.169.3.1145

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Cutting edge: molecular mechanisms of synergy between CD40 and the B cell antigen receptor: role for TNF receptor-associated factor 2 in receptor interaction

Journal article

Peer reviewed

Cutting edge: molecular mechanisms of synergy between CD40 and the B cell antigen receptor: role for TNF receptor-associated factor 2 in receptor interaction

Sokol A Haxhinasto, Bruce S Hostager and Gail A Bishop

The Journal of immunology (1950), Vol.169(3), pp.1145-1149

08/01/2002

DOI: 10.4049/jimmunol.169.3.1145

PMID: 12133933

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Abstract

Optimal Ag-specific B lymphocyte activation requires both recognition of Ag by the B cell Ag receptor (BCR) and contact-mediated interactions with Ag-specific Th lymphocytes. One of these interactions involves ligation of B cell CD40 by T cell-expressed CD154. CD40 signaling is crucial for Ab production, isotype switching, up-regulation of surface molecules, development of germinal centers, and the humoral memory response. The signaling pathways emanating from the BCR and CD40 are able to cooperate, but the molecular mechanisms responsible for this interaction are incompletely understood. The present study explored the roles of signaling motifs in the CD40 cytoplasmic tail in this synergy. We find that threonine in the PXQXT motif in the TNFR-associated factor-2 binding site is critical for synergistic effects of CD40 and BCR signals, independent of its phosphorylation. Furthermore, data suggest an indirect role for TNFR-associated factor-2 in the cooperative signaling.

Amino Acid Sequence

CD40 Antigens - physiology

Cell Line

Proteins - physiology

Lymphocyte Activation

Molecular Sequence Data

TNF Receptor-Associated Factor 2

TNF Receptor-Associated Factor 3

CD40 Antigens - chemistry

Animals

B-Lymphocytes - immunology

Receptors, Antigen, B-Cell - physiology

Mice

Details

Title: Subtitle: Cutting edge: molecular mechanisms of synergy between CD40 and the B cell antigen receptor: role for TNF receptor-associated factor 2 in receptor interaction
Creators: Sokol A Haxhinasto - Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Bruce S Hostager
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.169(3), pp.1145-1149
DOI: 10.4049/jimmunol.169.3.1145
PMID: 12133933
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI49993 / NIAID NIH HHS AI28847 / NIAID NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 08/01/2002
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001120902771

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