Expression of a V Region-Less B Cell Receptor Confers a Tolerance-Like Phenotype on Transgenic B Cells
| Autor: | Aimé Vazquez, Patrick Lorès, Alf Grandien, Daniel Corcos, Olga Dunda, Danielle Bucchini |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
T-Lymphocytes
Cellular differentiation Transgene Immunology B-cell receptor B-Lymphocyte Subsets Receptors Antigen B-Cell Apoptosis Mice Transgenic Biology Lymphocyte Activation Immunophenotyping Mice Growth factor receptor Immune Tolerance Animals Gene Rearrangement B-Lymphocyte Light Chain Humans Immunology and Allergy Transgenes Receptor Cells Cultured Crosses Genetic Clonal Anergy Mice Inbred BALB C Immunoglobulin mu-Chains Cell growth breakpoint cluster region Cell Differentiation Molecular biology Mice Inbred C57BL Proto-Oncogene Proteins c-bcl-2 Immunoglobulin Light Chains Binding domain |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.166.5.3083 |
| Popis: | Neoplastic B cells from H chain disease patients express a truncated B cell receptor (BCR), comprising a membrane Ig that lacks part of its extracellular domain. It has been speculated that deletion of the Ag binding domain would confer a constitutive activity on the BCR, as it has been shown for oncogenic growth factor receptors. A V region-less BCR has constitutive activity, because in transgenic mice it causes inhibition of endogenous H chain gene rearrangements and relieves the requirement for surrogate L chain in pre-B cell development. However, it has been speculated that normal Ag receptors also display constitutive activity. Here we show that transgenic B cells expressing a membrane H chain disease protein on their surface are phenotypically and functionally similar to B cells developing in the presence of their cognate Ag and that cells with normal levels of mutant BCR are eliminated in spleen via a bcl-2 sensitive pathway while progressing toward the mature stage. In contrast, cells with lower levels of mutant receptors develop as mature B cells. These findings support the view that the truncated BCR has a constitutive activity that mimics ligand binding, in analogy to what has been shown for oncogenic growth factor receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|