Lymphocyte-Specific Compensation for XLF/Cernunnos End-Joining Functions in V(D)J Recombination

Gang Li, Frederick W. Alt, Hwei Ling Cheng, James W. Brush, Peter H. Goff, Mike M. Murphy, Sonia Franco, Yu Zhang, Shan Zha

Research output: Contribution to journalArticle

Abstract

Mutations in XLF/Cernunnos (XLF) cause lymphocytopenia in humans, and various studies suggest an XLF role in classical nonhomologous end joining (C-NHEJ). We now find that XLF-deficient mouse embryonic fibroblasts are ionizing radiation (IR) sensitive and severely impaired for ability to support V(D)J recombination. Yet mature lymphocyte numbers in XLF-deficient mice are only modestly decreased. Moreover, XLF-deficient pro-B lines, while IR-sensitive, perform V(D)J recombination at nearly wild-type levels. Correspondingly, XLF/p53-double-deficient mice are not markedly prone to the pro-B lymphomas that occur in previously characterized C-NHEJ/p53-deficient mice; however, like other C-NHEJ/p53-deficient mice, they still develop medulloblastomas. Despite nearly normal V(D)J recombination in developing B cells, XLF-deficient mature B cells are moderately defective for immunoglobulin heavy-chain class switch recombination. Together, our results implicate XLF as a C-NHEJ factor but also indicate that developing mouse lymphocytes harbor cell-type-specific factors/pathways that compensate for the absence of XLF function during V(D)J recombination.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalMolecular Cell
Volume31
Issue number5
DOIs
StatePublished - Sep 5 2008

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V(D)J Recombination
Lymphocytes
Ionizing Radiation
B-Lymphocytes
Immunoglobulin Heavy Chains
Lymphopenia
Medulloblastoma
Lymphocyte Count
Genetic Recombination
Lymphoma
Fibroblasts
Mutation

Keywords

  • DNA
  • MOLIMMUNO

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Li, G., Alt, F. W., Cheng, H. L., Brush, J. W., Goff, P. H., Murphy, M. M., ... Zha, S. (2008). Lymphocyte-Specific Compensation for XLF/Cernunnos End-Joining Functions in V(D)J Recombination. Molecular Cell, 31(5), 631-640. https://doi.org/10.1016/j.molcel.2008.07.017

Lymphocyte-Specific Compensation for XLF/Cernunnos End-Joining Functions in V(D)J Recombination. / Li, Gang; Alt, Frederick W.; Cheng, Hwei Ling; Brush, James W.; Goff, Peter H.; Murphy, Mike M.; Franco, Sonia; Zhang, Yu; Zha, Shan.

In: Molecular Cell, Vol. 31, No. 5, 05.09.2008, p. 631-640.

Research output: Contribution to journalArticle

Li, G, Alt, FW, Cheng, HL, Brush, JW, Goff, PH, Murphy, MM, Franco, S, Zhang, Y & Zha, S 2008, 'Lymphocyte-Specific Compensation for XLF/Cernunnos End-Joining Functions in V(D)J Recombination', Molecular Cell, vol. 31, no. 5, pp. 631-640. https://doi.org/10.1016/j.molcel.2008.07.017
Li, Gang ; Alt, Frederick W. ; Cheng, Hwei Ling ; Brush, James W. ; Goff, Peter H. ; Murphy, Mike M. ; Franco, Sonia ; Zhang, Yu ; Zha, Shan. / Lymphocyte-Specific Compensation for XLF/Cernunnos End-Joining Functions in V(D)J Recombination. In: Molecular Cell. 2008 ; Vol. 31, No. 5. pp. 631-640.
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