Journal article
Characterization of CD40 signaling determinants regulating nuclear factor-kappa B activation in B lymphocytes
The Journal of immunology (1950), Vol.159(10), pp.4898-4906
11/15/1997
DOI: 10.4049/jimmunol.159.10.4898
PMID: 9366415
Abstract
CD40 signaling to B cells is important for generating an effective humoral immune response. CD40 ligation leads to B cell activation events such as proliferation, Ig secretion, isotype switching, and up-regulation of cell surface molecules, as well as the generation of memory B cells. Many of these events are dependent upon the ability of CD40 to activate the transcription factor NF-kappa B (NF-kappa B). To define the CD40 signaling components upstream of NF-kappa B activation and the functional consequences downstream of NF-kappa B activation, we examined mouse B cell transfectants expressing wild-type or mutant human CD40. Analysis of CD40 cytoplasmic domain truncation and point mutants defined a 10-amino acid CD40 cytoplasmic signaling determinant required for NF-kappa B activation. A threonine residue at position 234, previously shown to be important for CD40 association with TNF receptor-associated factor 2 (TRAF2), TRAF3, and TRAF5, was not required for NF-kappa B activation. This suggests that in B cells, CD40-induced NF-kappa B activation can occur independently of TRAF2 and TRAF5 association. NF-kappa B activation was independent of the transmembrane domain of CD40, suggesting that it is independent of p23, a molecule that associates with CD40 in a region other than the cytoplasmic domain. Proteasome-dependent inhibitory kappa B alpha (I kappa B alpha) and I kappa B beta degradation occurred downstream of CD40 ligation and preceded CD40-mediated NF-kappa B nuclear translocation. CD40- or pervanadate-mediated I kappa B tyrosine phosphorylation was not detected. NF-kappa B activation correlated with the ability of CD40 to induce Ab secretion and the up-regulation of ICAM-1 and LFA-1. However, NF-kappa B activation was insufficient for CD40-mediated up-regulation of B7-1, Fas, and CD23.
Details
- Title: Subtitle
- Characterization of CD40 signaling determinants regulating nuclear factor-kappa B activation in B lymphocytes
- Creators
- Yina Hsing - The Immunology Graduate Program, University of Iowa, Iowa City 52242, USABruce S HostagerGail A Bishop
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.159(10), pp.4898-4906
- Publisher
- United States
- DOI
- 10.4049/jimmunol.159.10.4898
- PMID
- 9366415
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Grant note
- AI28847 / NIAID NIH HHS CA66570 / NCI NIH HHS DK25295 / NIDDK NIH HHS
- Language
- English
- Date published
- 11/15/1997
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001226902771
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