Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b

Bruce S Hostager; Gail A Bishop

doi:10.4049/jimmunol.168.7.3318

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Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b

Journal article

Peer reviewed

Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b

Bruce S Hostager and Gail A Bishop

The Journal of immunology (1950), Vol.168(7), pp.3318-3322

04/01/2002

DOI: 10.4049/jimmunol.168.7.3318

PMID: 11907088

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Abstract

TNFR-associated factors (TRAFs) participate in the signaling of many TNFR family members, including CD40, CD120a (TNFR1), and CD120b (TNFR2). Previously, we found that a dominant-negative TRAF2 molecule inhibits CD40-mediated Ab secretion by the mouse B cell line CH12.LX. However, disruption of the TRAF2 binding site in the cytoplasmic domain of CD40 does not diminish the ability of CD40 to stimulate Ab secretion, nor is this mutation able to circumvent the inhibition of Ab secretion by dominant-negative TRAF2. Here we demonstrate that CD40-induced TNF stimulates IgM production through CD120b and that CD120b signaling is required for optimal CD40-induced IgM secretion. Furthermore, although both CD40 and CD120b can bind TRAF2, TRAF2-dependent CD40 signals cannot substitute for TRAF2-dependent CD120b signals in the activation of IgM secretion. Our results indicate a potentially important role for CD120b in the activation of IgM secretion and that TRAF2 is used by CD40 and CD120b in distinct ways.

Protein Binding - genetics

Humans

Receptors, Tumor Necrosis Factor - physiology

TNF Receptor-Associated Factor 2

Signal Transduction - immunology

CD40 Antigens - metabolism

Transfection

Receptors, Tumor Necrosis Factor, Type II

CD40 Antigens - genetics

Cytoplasm - genetics

B-Lymphocytes - metabolism

CD40 Antigens - physiology

Cell Line

Proteins - physiology

Mice, Inbred C57BL

Receptors, Tumor Necrosis Factor, Type I

Protein Structure, Tertiary - genetics

Signal Transduction - genetics

Protein Binding - immunology

Proteins - genetics

Tumor Necrosis Factor-alpha - pharmacology

Animals

B-Lymphocytes - immunology

Proteins - metabolism

Cytoplasm - immunology

Tumor Necrosis Factor-alpha - physiology

Antigens, CD - physiology

Mice

Tumor Necrosis Factor-alpha - biosynthesis

Immunoglobulin M - biosynthesis

Details

Title: Subtitle: Role of TNF receptor-associated factor 2 in the activation of IgM secretion by CD40 and CD120b
Creators: Bruce S Hostager - Department of Microbiology, University of Iowa, and Veterans Affairs Medical Center, Iowa City, IA 52242, USA
Gail A Bishop
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.168(7), pp.3318-3322
DOI: 10.4049/jimmunol.168.7.3318
PMID: 11907088
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI28847 / NIAID NIH HHS CA66570 / NCI NIH HHS DK25295 / NIDDK NIH HHS
Language: English
Date published: 04/01/2002
Academic Unit: Microbiology and Immunology; President
Record Identifier: 9984001224802771

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