Impaired Light Chain Allelic Exclusion and Lack of Positive Selection in Immature B Cells Expressing Incompetent Receptor Deficient of CD19
| Autor: | Doron Melamed, Shoham Shivtiel, Nira Leider, Zaki Kraiem, Orit Sadeh |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Transgene
Antigens CD19 Immunology Population Receptors Antigen B-Cell Gene Rearrangement T-Lymphocyte CD19 Mice hemic and lymphatic diseases medicine Animals Immunology and Allergy education Receptor Alleles Cells Cultured B cell B-Lymphocytes education.field_of_study biology breakpoint cluster region Molecular biology Allelic exclusion medicine.anatomical_structure biology.protein Calcium Immunoglobulin Light Chains Bone marrow |
| Zdroj: | The Journal of Immunology. 168:5596-5604 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Positive signaling is now thought to be important for B cell maturation, although the nature of such signals has not yet been defined. We are studying the regulatory role of B cell Ag receptor (BCR) signaling in mediating positive selection of immature B cells. To do so, we use Ig transgenic mice (3-83Tg) that are deficient in CD19, thus generating a monoclonal immature B cell population expressing signaling-incompetent BCR. Immature 3-83Tg CD19−/− B cells undergo developmental arrest in the bone marrow, allowing maturation only to cells that effectively compensate for the compromised receptor by elevated levels of BCR. We find that developmentally arrested 3-83Tg CD19−/− B cells fail to impose L chain allelic exclusion and undergo intensive V(D)J recombination to edit their BCR. Furthermore, immature 3-83Tg CD19−/− B cells, which were grown in vitro, failed to undergo positive selection and to survive when adoptively transferred into normal recipients. However, elevation of BCR expression levels, obtained by transgene homozygosity, effectively compensated for the compromised BCR and completely restored BCR-mediated Ca2+ influx, allelic exclusion, and positive selection. Our results suggest that the BCR signaling threshold mediates positive selection of developing B cells, and that a receptor-editing mechanism has an important role in rescuing cells that fail positive selection because of incompetent receptors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|