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

Immunologic Research
Nahum Puebla-Osorio, Chengming Zhu

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 maintenanc...Continue Reading

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Citations

May 10, 2012·Immunologic Research·Shruti MaluPatricia Cortes
Jan 13, 2012·Annals of the New York Academy of Sciences·Noel Fcc de MirandaQiang Pan-Hammarström
Sep 3, 2011·European Journal of Haematology·Annette VangstedUlla Vogel
Mar 5, 2011·Molecular Carcinogenesis·Claudia M MonroyRanda El-Zein
Feb 15, 2018·Blood·Anand S BhagwatChristopher R Vakoc
Oct 16, 2019·Immunology and Cell Biology·Timothy M Johanson, Rhys S Allan
Mar 31, 2019·Nature Reviews. Immunology·Timothy M JohansonRhys S Allan

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