| First Author | Nicolas L | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 11 | Pages | 3137-3142 |
| PubMed ID | 31028119 | Mgi Jnum | J:275473 |
| Mgi Id | MGI:6306162 | Doi | 10.4049/jimmunol.1801033 |
| Citation | Nicolas L, et al. (2019) Cutting Edge: ATM Influences Germinal Center Integrity. J Immunol 202(11):3137-3142 |
| abstractText | 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. |
