Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells
| Autor: | Sandy R. Larson, Mark J. Shlomchik, John C. Cambier, Nicole A. Beavers, Andrew Getahun |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer animal structures Phosphoric monoester hydrolases Immunology chemical and pharmacologic phenomena Mice Transgenic Protein tyrosine phosphatase Biology 030204 cardiovascular system & hematology Inhibitory postsynaptic potential Article Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Lupus Erythematosus Systemic Immunology and Allergy Research Articles 030304 developmental biology Clonal Anergy B-Lymphocytes 0303 health sciences Protein Tyrosine Phosphatase Non-Receptor Type 6 technology industry and agriculture PTEN Phosphohydrolase breakpoint cluster region hemic and immune systems Cell Biology Cell biology 3. Good health src-Family Kinases 030104 developmental biology Phosphatidylinositol-3 4 5-Trisphosphate 5-Phosphatases embryonic structures Signal transduction Cell activation Function (biology) Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Cambier et al. show that the tyrosine phosphatase SHP-1 and the inositol phosphatase SHIP-1 are required to maintain B cell anergy. Many autoreactive B cells persist in the periphery in a state of unresponsiveness called anergy. This unresponsiveness is rapidly reversible, requiring continuous BCR interaction with self-antigen and resultant regulatory signaling for its maintenance. Using adoptive transfer of anergic B cells with subsequent acute induction of gene deletion or expression, we demonstrate that the continuous activities of independent inhibitory signaling pathways involving the tyrosine phosphatase SHP-1 and the inositol phosphatase SHIP-1 are required to maintain anergy. Acute breach of anergy by compromise of either of these pathways leads to rapid cell activation, proliferation, and generation of short-lived plasma cells that reside in extrafollicular foci. Results are consistent with predicted/observed reduction in the Lyn–SHIP-1–PTEN–SHP-1 axis function in B cells from systemic lupus erythematosus patients. |
| Databáze: | OpenAIRE |
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