Cutting Edge: ATM Influences Germinal Center Integrity.
J Immunol
; 202(11): 3137-3142, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-31028119
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 BT 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Linfócitos T
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Centro Germinativo
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Proteínas Mutadas de Ataxia Telangiectasia
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2019
Tipo de documento:
Article