Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion

Hiromi Mori, Rika Ouchida, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Yingqian Li, Xiang Gao, Akira Yasui, R. Stephen Lloyd, Ji Yang Wang

    Research output: Contribution to journalArticle

    19 Citations (Scopus)

    Abstract

    Mammalian cells possess multiple DNA glycosylases, including OGG1, NTH1, NEIL1, NEIL2 and NEIL3, for the repair of oxidative DNA damage. Among these, NEIL1 and NEIL2 are able to excise oxidized bases on single stranded or bubble-structured DNA and has been implicated in repair of oxidative damage associated with DNA replication or transcription. We found that Neil1 was highly constitutively expressed in the germinal center (GC) B cells, a rapidly dividing cell population that is undergoing immunoglobulin (Ig) gene hypermutation and isotype switching. While Neil1-/- mice exhibited normal B and T cell development and maturation, these mice contained a significantly lower frequency of GC B cells than did WT mice after immunization with a T-dependent antigen. Consistent with the reduced expansion of GC B cells, Neil1-/- mice had a decreased frequency of Ig gene hypermutation and produced less antibody against a T-dependent antigen during both primary and secondary immune responses. These results suggest that repair of endogenous oxidative DNA damage by NEIL1 is important for the rapid expansion of GC B cells and efficient induction of humoral immune responses.

    Original languageEnglish
    Pages (from-to)1328-1332
    Number of pages5
    JournalDNA Repair
    Volume8
    Issue number11
    DOIs
    Publication statusPublished - 2009 Nov 2

    Keywords

    • DNA glycosylase
    • Germinal center B cells
    • Immune response
    • Oxidative damage
    • Somatic hypermutation

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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  • Cite this

    Mori, H., Ouchida, R., Hijikata, A., Kitamura, H., Ohara, O., Li, Y., Gao, X., Yasui, A., Lloyd, R. S., & Wang, J. Y. (2009). Deficiency of the oxidative damage-specific DNA glycosylase NEIL1 leads to reduced germinal center B cell expansion. DNA Repair, 8(11), 1328-1332. https://doi.org/10.1016/j.dnarep.2009.08.007