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Although error-free repair by homologous recombination (HR) is crucial to prevent excessive DNA strand breakage at activation-induced cytidine deaminase off-target genes, its role at the hypermutating Ig locus in the germinal center is unexplored. Using B cell\u2013specific inactivation of the critical HR factor Brca2, we detected decreased proliferation, survival, and thereby class switching of ex vivo\u2013activated B cells. Intriguingly, an HR defect allowed for a germinal center reaction and affinity maturation in vivo, albeit at reduced amounts. Analysis of SHM revealed that a certain fraction of DNA lesions at C:G bp was indeed repaired in an error-free manner via Brca2 instead of being processed by error-prone translesion polymerases. By applying a novel pseudo-time in silico analysis of mutational processes, we found that the activity of A:T mutagenesis during SHM increased during a germinal center reaction, but this was in part defective in Brca2-deficient mice. These mutation pattern changes in Brca2-deficient B cells were mostly specific for the Ig V region, suggesting a local or time-dependent need for recombination repair to survive high rates of SHM and especially A:T mutagenesis.<\/jats:p>","DOI":"10.4049\/jimmunol.1900483","type":"journal-article","created":{"date-parts":[[2019,8,9]],"date-time":"2019-08-09T19:55:14Z","timestamp":1565380514000},"page":"1493-1501","source":"Crossref","is-referenced-by-count":7,"title":["Regulation of the Germinal Center Reaction and Somatic Hypermutation Dynamics by Homologous Recombination"],"prefix":"10.1093","volume":"203","author":[{"given":"Gianna","family":"Hirth","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Institute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich Schiller University , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9723-9063","authenticated-orcid":false,"given":"Carl-Magnus","family":"Svensson","sequence":"additional","affiliation":[{"name":"Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"B\u00f6ttcher","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Institute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich Schiller University , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Ullrich","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Institute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich Schiller University , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Thilo","family":"Figge","sequence":"additional","affiliation":[{"name":"Research Group Applied Systems Biology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Kn\u00f6ll Institute , 07745 Jena ,","place":["Germany"]},{"name":"Faculty of Biological Sciences, Friedrich Schiller University , 07743 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berit","family":"Jungnickel","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Institute of Biochemistry and Biophysics, Faculty of Biological Sciences, Friedrich Schiller University , 07745 Jena ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,15]]},"reference":[{"key":"2025030417542122000_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.biochem.76.061705.090740","article-title":"Molecular mechanisms of antibody somatic hypermutation","volume":"76","author":"Di Noia","year":"2007","journal-title":"Annu. 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