Immunologic Research

, Volume 41, Issue 2, pp 103–122

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


DOI: 10.1007/s12026-008-8015-3

Cite this article as:
Puebla-Osorio, N. & Zhu, C. Immunol Res (2008) 41: 103. doi:10.1007/s12026-008-8015-3


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.


V(D)J recombination Class switch recombination Somatic hypermutation RAG1/RAG2 AID DNA damage response Non-homologous end-joining Alternative end-joining Genomic instability Lymphoma 

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Department of ImmunologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.The University of Texas Graduate School of Biomedical Science at HoustonHoustonUSA