Article: Impaired V(D)J recombination and increased apoptosis among B cell precursors in the bone marrow of c-Abl-deficient mice.
2007 Volume 19, Issue 3, Page(s) 267–276
Abstract: Previous studies on c-Abl-deficient mice have shown high post-natal mortality and lymphopenia. However, the mechanisms by which c-Abl may influence B lymphopoiesis remain obscure. In this study, we analyzed B cell sub-populations at various ... ...
| Abstract | Previous studies on c-Abl-deficient mice have shown high post-natal mortality and lymphopenia. However, the mechanisms by which c-Abl may influence B lymphopoiesis remain obscure. In this study, we analyzed B cell sub-populations at various differentiation stages in the bone marrow (BM) of c-Abl-deficient mice. Phenotypic analyses revealed that c-Abl(-/-) pro-B cells were reduced to half of normal incidence and absolute number, while pre-B cells showed an even greater reduction. Both c-Abl(-/-) pro-B and pre-B cell populations showed considerably elevated apoptosis ex vivo and in short-term culture but their cell cycle progression was not impaired. In contrast, apoptosis of immature IgM(+)IgD(-) B lymphocytes remained at normal control levels. Inhibition of c-Abl activity by STI571 in normal BM cultures significantly increased apoptosis in B cell precursors while the survival of immature B cells was not affected. To determine whether c-Abl deficiency affects Ig heavy-chain rearrangement, we found that the frequency of V(D)J recombination was markedly reduced by 15-fold in c-Abl(-/-) pro-B cells compared with the control values. However, no perturbation in the levels of signal-end recombination intermediates was found. Taken together, we propose that c-Abl mediates a stage-specific anti-apoptotic response in precursor B cells and is required for efficient V(D)J recombination during B cell development. |
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| MeSH term(s) | Animals ; Apoptosis/genetics ; B-Lymphocytes/cytology ; B-Lymphocytes/metabolism ; Bone Marrow Cells/cytology ; Bone Marrow Cells/metabolism ; Cell Cycle/genetics ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Cells, Cultured ; Gene Rearrangement, B-Lymphocyte ; Immunoglobulin Heavy Chains/genetics ; Lymphopoiesis/genetics ; Mice ; Mice, Knockout ; Phenotype ; Proto-Oncogene Proteins c-abl/deficiency ; Proto-Oncogene Proteins c-abl/genetics ; Recombination, Genetic ; VDJ Recombinases/metabolism |
| Chemical Substances | Immunoglobulin Heavy Chains ; Proto-Oncogene Proteins c-abl (EC 2.7.10.2) ; VDJ Recombinases (EC 2.7.7.-) |
| Language | English |
| Publishing date | 2007-03 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1013745-2 |
| ISSN | 1460-2377 ; 0953-8178 |
| ISSN (online) | 1460-2377 |
| ISSN | 0953-8178 |
| DOI | 10.1093/intimm/dxl143 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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