Interleukin (IL)-4-independent immunoglobulin class switch to immunoglobulin (Ig)E in the mouse
| Autor: | Werner Müller, R.A. Morawetz, R L Coffman, T M Doherty, Fred D. Finkelman, Lucia Gabriele, Ralf Kühn, Luiz Vicente Rizzo, Herbert C. Morse, Nancy Noben-Trauth, Klaus Rajewsky |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
medicine.drug_class
Immunology Immunoglobulin E Monoclonal antibody Immunoglobulin D Dinoprostone Interferon-gamma Mice Murine Acquired Immunodeficiency Syndrome medicine Animals Immunology and Allergy RNA Messenger Nippostrongylus brasiliensis Interleukin 4 Strongylida Infections Recombination Genetic biology Interleukin Articles biology.organism_classification Immunoglobulin Class Switching Mice Mutant Strains Mice Inbred C57BL Immunoglobulin class switching biology.protein Interleukin-4 Antibody |
| Zdroj: | The Journal of Experimental Medicine Scopus-Elsevier |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.184.5.1651 |
| Popis: | Immunoglobulin (Ig) class switching in B cells is regulated by stimuli transduced by cytokines and cell-cell contact. Among these stimuli, interleukin (IL)-4 has been considered an absolute prerequisite for class switching to IgE in the mouse. Here we report that IL-4-deficient (IL-4-/-) and wildtype mice had comparably elevated serum IgE levels during the course of a murine retrovirus-induced immunodeficiency syndrome, MAIDS. IgE switching in IL-4-/- mice was also induced by injection of anti-IgD antibody. Treatment with anti-IgD induced germline epsilon (g epsilon) transcripts with comparable efficiency in IL-4-/- mice and controls, but the levels of productive epsilon transcripts (p epsilon) were lower by a factor of 200 and serum IgE levels were lower by a factor of 300 in IL-4-/- mice as compared with controls. Induction of g epsilon after anti-IgD treatment of IL-4-/- mice was unaffected by simultaneous treatment with monoclonal antibodies to IL-4 and IL-4 receptor alpha chain. Infection of IL-4-/- mice with Nippostrongylus brasiliensis, a potent stimulus for IgE production, resulted in induction of g epsilon transcripts; however, p epsilon transcripts were barely detectable and serum IgE was not detected. These findings establish a novel IL-4-independent pathway for IgE switching in the mouse that is strongly activated in retroviral infection but weakly in nematode infection. This pathway appears to be dependent on distinct factors that separately control induction of g epsilon transcription and switch recombination to p epsilon. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|