Impaired IgE response in SWAP-70-deficient mice

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Protein SWAP-70 was initially isolated from nuclei of activated B cells and was implicated in the immunoglobulin class switch process. After B cell activation the protein translocates from the cytoplasm to the nucleus, and may serve to signal nuclear processes. We have generated mice deficient in SWAP-70 and found three main differences when compared to wild-type mice: (i) their B lymphocytes are two- to threefold more sensitive to gamma-irradiation than B cells of wild type; (ii) SWAP-70-deficient mice developed autoantibodies at a much higher frequency; and (iii) the CD40 signaling pathway is compromised in the mutant mice. CD40-dependent switching to the IgE isotype is reduced five- to eightfold in vitro. In SWAP-70-deficient mice, IgE levels prior to immunization were six- to sevenfold lower than in wild-type mice, and after immunization three- to fourfold lower. CD40-induced proliferation was transiently increased in the mutant. LPS-induced switching to other isotypes, however, and LPS-induced proliferation were normal. We propose that SWAP-70 serves a specific role in the CD40 signaling pathway, in particular in the IgE response.

Details

Original languageEnglish
Pages (from-to)2467-75
Number of pages9
JournalEuropean Journal of Immunology
Volume31
Issue number8
Publication statusPublished - Aug 2001
Peer-reviewedYes

External IDs

Scopus 0034857273

Keywords

Keywords

  • Animals, Apoptosis, Autoantibodies/biosynthesis, B-Lymphocytes/cytology, CD40 Antigens/immunology, Cell Division, DNA-Binding Proteins/deficiency, Gamma Rays, Gene Targeting, Guanine Nucleotide Exchange Factors, Immunoglobulin Class Switching/genetics, Immunoglobulin E/biosynthesis, Immunoglobulin G/biosynthesis, Lipopolysaccharides/immunology, Lymphocyte Activation, Mice, Mice, Knockout, Minor Histocompatibility Antigens, Mutation/genetics, Nuclear Proteins/deficiency, Radiation Tolerance, Signal Transduction