Impaired IgE response in SWAP-70-deficient mice.
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.
Borggrefe
T
T
Basel Institute for Immunology, Basel, Switzerland.
Keshavarzi
S
S
Gross
B
B
Wabl
M
M
Jessberger
R
R
D000818:Animals; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D019013:CD40 Antigens / Q000276:immunology*; D002455:Cell Division; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D005720:Gamma Rays; D018390:Gene Targeting; D020662:Guanine Nucleotide Exchange Factors; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D015778:Minor Histocompatibility Antigens; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D011836:Radiation Tolerance; D015398:Signal Transduction
D001323:Autoantibodies; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; C113365:Swap70 protein, mouse; D007073:Immunoglobulin E