| Autor: |
Lam QL; Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong, China., Lo CK, Zheng BJ, Ko KH, Osmond DG, Wu GE, Rottapel R, Lu L |
| Jazyk: |
angličtina |
| Zdroj: |
International immunology [Int Immunol] 2007 Mar; Vol. 19 (3), pp. 267-76. Date of Electronic Publication: 2007 Jan 17. |
| DOI: |
10.1093/intimm/dxl143 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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