AI Article Synopsis
- The study investigates the role of the ATM protein in B cells during immune responses, specifically focusing on its impact in vivo.
- Researchers found that mice with B cell-specific deletion of ATM had fewer and smaller germinal centers (GCs) after immunization, leading to issues in antibody production.
- The findings highlight that ATM is crucial for resolving DNA damage in B cells, as its absence results in increased cell death and impaired immune response efficiency.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529280 | PMC |
| http://dx.doi.org/10.4049/jimmunol.1801033 | DOI Listing |
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