Independent and opposing roles for Btk and lyn in B and myeloid signaling pathways
| Autor: | Satterthwaite, AB, Lowell, CA, Khan, WN, Sideras, P, Alt, FW, Witte, ON |
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| Rok vydání: | 1998 |
| Předmět: |
Knockout
Immunology Inbred Strains Immunoglobulins Src family kinases transgenic mice Inbred C57BL environment and public health Medical and Health Sciences Autoimmune Diseases Mice immune system diseases Agammaglobulinemia hemic and lymphatic diseases Lymphopenia Receptors B cell development Agammaglobulinaemia Tyrosine Kinase Animals Lymphocyte Count Inbred BALB C B-Lymphocytes B cell receptor B-Cell hemic and immune systems Protein-Tyrosine Kinases Hematopoietic Stem Cells Hematopoiesis Immunoglobulin Isotypes src-Family Kinases Antigen biological phenomena cell phenomena and immunity immunodeficiency Signal Transduction |
| Zdroj: | The Journal of experimental medicine, vol 188, iss 5 |
| Popis: | Transphosphorylation by Src family kinases is required for the activation of Bruton's tyrosine kinase (Btk). Differences in the phenotypes of Btk-/- and lyn-/- mice suggest that these kinases may also have independent or opposing functions. B cell development and function were examined in Btk-/-lyn-/- mice to better understand the functional interaction of Btk and Lyn in vivo. The antigen-independent phase of B lymphopoiesis was normal in Btk-/-lyn-/- mice. However, Btk-/-lyn-/- animals had a more severe immunodeficiency than Btk-/- mice. B cell numbers and response to T cell-dependent antigens were reduced. Btk and Lyn therefore play independent or partially redundant roles in the maintenance and function of peripheral B cells. Autoimmunity, hypersensitivity to B cell receptor (BCR) cross-linking, and splenomegaly caused by myeloerythroid hyperplasia were alleviated by Btk deficiency in lyn-/- mice. A transgene expressing Btk at approximately 25% of endogenous levels (Btklo) was crossed onto Btk-/- and Btk-/-lyn-/- backgrounds to demonstrate that Btk is limiting for BCR signaling in the presence but not in the absence of Lyn. These observations indicate that the net outcome of Lyn function in vivo is to inhibit Btk-dependent pathways in B and myeloid cells, and that Btklo mice are a useful sensitized system to identify regulatory components of Btk signaling pathways. |
| Databáze: | OpenAIRE |
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