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DNA damage and repair during lymphoid development: antigen receptor diversity, genomic integrity and lymphomagenesis

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Abstract

Lymphocyte maturation requires generation of a large diversity of antigen receptors, which involves somatic rearrangements at the antigen receptor genes in a process termed V(D)J recombination. Upon encountering specific antigens, B-lymphocytes undergo rearrangements in the constant region of the immunoglobulin genes to optimize immune responses in a process called class switch recombination. Activated B-cells also undergo somatic hypermutation in the variable regions of the immunoglobulin genes to enhance their antigenic affinity. These somatic events are initiated by the infliction of DNA lesions within the antigen receptor genes that are strictly confined to a specific developmental window and cell-cycle stage. DNA lesions are then repaired by one of the general DNA repair mechanisms, such as non-homologous end-joining. Mutations in key factors of these pathways lead to the interruption of these processes and immunodeficiency, making it possible to study the mechanisms of cellular response to DNA lesions and their repair. This review briefly summarizes some of the recently developed animal models with focus on current advances in the understanding of the mechanism of DNA end-joining activities, and its role in the maintenance of genomic stability and the prevention of tumorigenesis.

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Acknowledgements

We would like to thank Melanie Dujka, Omid Tavana and Drs. Phillip Carpenter and Cara Benjamin for their critical review of this manuscript. Our work is supported by the American Cancer Society and the National Cancer Institute (to C.Z.).

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  1. Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77054, USA

    Nahum Puebla-Osorio & Chengming Zhu

  2. The University of Texas Graduate School of Biomedical Science at Houston, Houston, TX, 77030, USA

    Chengming Zhu

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  1. Nahum Puebla-Osorio
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Correspondence to Chengming Zhu.

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Puebla-Osorio, N., Zhu, C. DNA damage and repair during lymphoid development: antigen receptor diversity, genomic integrity and lymphomagenesis. Immunol Res 41, 103–122 (2008). https://doi.org/10.1007/s12026-008-8015-3

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