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Cutting Edge: ATM Influences Germinal Center Integrity.


ABSTRACT: The DNA damage response protein ATM has long been known to influence class switch recombination in ex vivo-cultured B cells. However, an assessment of B cell-intrinsic requirement of ATM in humoral responses in vivo was confounded by the fact that its germline deletion affects T cell function, and B:T cell interactions are critical for in vivo immune responses. In this study, we demonstrate that B cell-specific deletion of ATM in mice leads to reduction in germinal center (GC) frequency and size in response to immunization. We find that loss of ATM induces apoptosis of GC B cells, likely due to unresolved DNA lesions in cells attempting to undergo class-switch recombination. Accordingly, suboptimal GC responses in ATM-deficient animals are characterized by decreased titers of class-switched Abs and decreased rates of somatic hypermutation. These results unmask the critical B cell-intrinsic role of ATM in maintaining an optimal GC response following immunization.

SUBMITTER: Nicolas L 

PROVIDER: S-EPMC6529280 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Cutting Edge: ATM Influences Germinal Center Integrity.

Nicolas Laura L   Cols Montserrat M   Smolkin Ryan R   Fernandez Keith C KC   Yewdell William T WT   Yen Wei-Feng WF   Zha Shan S   Vuong Bao Q BQ   Chaudhuri Jayanta J  

Journal of immunology (Baltimore, Md. : 1950) 20190426 11


The DNA damage response protein ATM has long been known to influence class switch recombination in ex vivo-cultured B cells. However, an assessment of B cell-intrinsic requirement of ATM in humoral responses in vivo was confounded by the fact that its germline deletion affects T cell function, and B:T cell interactions are critical for in vivo immune responses. In this study, we demonstrate that B cell-specific deletion of ATM in mice leads to reduction in germinal center (GC) frequency and size  ...[more]

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