Impairment of antigen-specific antibody production in transgenic mice expressing a dominant-negative form of gp130.
gp130 is a common signal-transducing receptor component for the interleukin 6 family of cytokines functioning in, for example, immune, hematopoietic, and nervous systems. In this study, to investigate the physiological functions of gp130 and to determine the pathological consequences of impaired gp130 signals, we have generated transgenic mice expressing a cytoplasmically truncated form of mouse gp130. Expression of this form of gp130 in lymphocytes significantly suppressed interleukin 6-induced tyrosine phosphorylation of endogenous gp130 and a downstream signaling molecule, signal transducer and activator of transcription 3, indicating that this form has a dominant negative function. In spite of the impaired gp130 signals, the development of lymphocytes in the transgenic mice appeared normal in terms of surface marker phenotypes. These mice, however, exhibited severe defects in antigen-specific antibody production of most immunoglobulin isotypes other than IgM after immunization with 2,4-dinitrophenol-conjugated ovalbumin. These results demonstrate in vivo that gp130 is essential for antigen-specific antibody production.
Kumanogoh
A
A
Department of Medicine III, Osaka University Medical School, Yamada-oka, Suita, Japan.
Marukawa
S
S
Kumanogoh
T
T
Hirota
H
H
Yoshida
K
K
Lee
I S
IS
Yasui
T
T
Yoshida
K
K
Taga
T
T
Kishimoto
T
T
D000199:Actins / Q000235:genetics; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D002645:Chickens; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004140:Dinitrophenols / Q000276:immunology; D005799:Genes, Dominant; D006241:Haptens; D015850:Interleukin-6 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D015534:Trans-Activators / Q000378:metabolism
D000199:Actins; D015703:Antigens, CD; D004268:DNA-Binding Proteins; D004140:Dinitrophenols; D006241:Haptens; C494200:Il6st protein, mouse; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C045521:dinitrophenol-ovalbumin; D050822:Cytokine Receptor gp130; D010047:Ovalbumin