Cutting edge: ATM influences germinal center integrity Journal Article
| Authors: | Nicolas, L.; Cols, M.; Smolkin, R.; Fernandez, K. C.; Yewdell, W. T.; Yen, W. F.; Zha, S.; Vuong, B. Q.; Chaudhuri, J. |
| Article Title: | 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. © 2019 by The American Association of Immunologists, Inc. |
| Journal Title: | Journal of Immunology |
| Volume: | 202 |
| Issue: | 11 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2019-06-01 |
| Start Page: | 3137 |
| End Page: | 3142 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1801033 |
| PUBMED: | 31028119 |
| PROVIDER: | scopus |
| PMCID: | PMC6529280 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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71Chaudhuri -
13Yen -
17Yewdell -
11Cols Vidal -
8Smolkin
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