Cutting Edge: ATM Influences Germinal Center Integrity.

Autor:	Nicolas L; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Cols M; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Smolkin R; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Fernandez KC; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065.; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065., Yewdell WT; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Yen WF; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065., Zha S; Institute for Cancer Genetics, Department of Pediatrics, Pathology and Cell Biology, Columbia University Medical Center, New York, NY 10032; and., Vuong BQ; Department of Biology, City College of New York, City University of New York, New York, NY 10031., Chaudhuri J; Immunology Program, Gerstner Sloan Kettering Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065; chaudhuj@mskcc.org.; Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, Cornell University, New York, NY 10065.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Jun 01; Vol. 202 (11), pp. 3137-3142. Date of Electronic Publication: 2019 Apr 26.
DOI:	10.4049/jimmunol.1801033
Abstrakt:	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. (Copyright © 2019 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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