Tonic BCR Signaling Represses Receptor Editing via Raf- and Calcium-dependent Signaling Pathways
| Autor: | Andrew T. Miller, Laura B. Ramsey, Michael P. Cooke, Amanda L. Vegoe, Michael A. Farrar |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Genetically modified mouse
Mice Knockout B-Lymphocytes Transgene Immunology B-cell receptor breakpoint cluster region Receptor editing Receptors Antigen B-Cell Biology Immunoglobulin light chain Molecular biology Article Immunoglobulin kappa-Chains Mice medicine.anatomical_structure medicine Immunology and Allergy Animals raf Kinases Calcium Signaling Signal transduction B cell |
| Popis: | Light chain receptor editing is an important mechanism that prevents B cell self-reactivity. We have previously shown that tonic signaling through the BCR represses RAG expression at the immature B cell stage, and that initiation of light chain rearrangements occurs in the absence of these tonic signals in an in vitro model of B cell development. To further test our hypothesis we studied the effect of itpkb deficiency (itpkb−/− mice) or Raf hyper-activation (Raf-CAAX transgenic mice), two mutations that enhance BCR signaling, on receptor editing in an in vivo model. This model relies on transferring bone marrow from wild-type or mutant mice into mice expressing an anti-kappa light chain transgene. The anti-kappa transgene induces receptor editing of all kappa light chain expressing B cells, leading to a high frequency of lambda light chain expressing B cells. Anti-κ transgenic recipients of bone marrow from itpkb−/− or Raf-CAAX mice showed lower levels of editing to λ light chain than did non-transgenic control recipients. These results provide evidence in an in vivo model that enhanced BCR signaling at the immature B cell stage of development suppresses light chain receptor editing. |
| Databáze: | OpenAIRE |
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