{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:50:09Z","timestamp":1787946609899,"version":"build-2784847793"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":3108,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Although common variable immunodeficiency (CVID) has long been considered as a group of primary Ab deficiencies, growing experimental data now suggest a global disruption of the entire adaptive immune response in a segment of patients. Oligoclonality of the TCR repertoire was previously demonstrated; however, the manner in which it relates to other B cell and T cell findings reported in CVID remains unclear. Using a combination approach of high-throughput TCR\u03b2 sequencing and multiparametric flow cytometry, we compared the TCR repertoire diversity between various subgroups of CVID patients according to their B cell immunophenotypes. Our data suggest that the reduction in repertoire diversity is predominantly restricted to those patients with severely reduced class-switched memory B cells and an elevated level of CD21lo B cells (Freiburg 1a), and may be driven by a reduced number of naive T cells unmasking underlying memory clonality. Moreover, our data indicate that this loss in repertoire diversity progresses with advancing age far exceeding the expected physiological rate. Radiological evidence supports the loss in thymic volume, correlating with the decrease in repertoire diversity. Evidence now suggests that primary thymic failure along with other well-described B cell abnormalities play an important role in the pathophysiology in Freiburg group 1a patients. Clinically, our findings emphasize the integration of combined B and T cell testing to identify those patients at the greatest risk for infection. Future work should focus on investigating the link between thymic failure and the severe reduction in class-switched memory B cells, while gathering longitudinal laboratory data to examine the progressive nature of the disease.<\/jats:p>","DOI":"10.4049\/jimmunol.1600526","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T02:28:28Z","timestamp":1470104908000},"page":"1642-1649","source":"Crossref","is-referenced-by-count":22,"title":["Accelerated Loss of TCR Repertoire Diversity in Common Variable Immunodeficiency"],"prefix":"10.1093","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-4051","authenticated-orcid":false,"given":"Gabriel K","family":"Wong","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, University of Birmingham , Edgbaston B15 2TT,","place":["United Kingdom"]},{"name":"West Midlands Primary Immunodeficiency Centre, Birmingham Heartlands Hospital , Birmingham B9 5SS,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0104-9303","authenticated-orcid":false,"given":"David","family":"Millar","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital , Boston MA 02114"},{"name":"Department of Medicine, Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Penny","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, University of Birmingham , Edgbaston B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1783-5181","authenticated-orcid":false,"given":"James M","family":"Heather","sequence":"additional","affiliation":[{"name":"Division of Infection and Immunity, University College London , London WC1E 6BT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punam","family":"Mistry","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, University of Birmingham , Edgbaston B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico","family":"Buettner","sequence":"additional","affiliation":[{"name":"Medical Research Council Centre for Immune Regulation, University of Birmingham , Edgbaston B15 2TT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Bryon","sequence":"additional","affiliation":[{"name":"Regional Genetics Laboratory, Birmingham Women\u2019s Hospital , Birmingham B15 2TG,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarnoud P","family":"Huissoon","sequence":"additional","affiliation":[{"name":"West Midlands Primary Immunodeficiency Centre, Birmingham Heartlands Hospital , Birmingham B9 5SS,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-4142","authenticated-orcid":false,"given":"Mark","family":"Cobbold","sequence":"additional","affiliation":[{"name":"Cancer Center, Massachusetts General Hospital , Boston MA 02114"},{"name":"Department of Medicine, Harvard Medical School , Charlestown, MA 02129"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,9,1]]},"reference":[{"key":"2025030617475296900_r1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/0167-5699(92)90043-7","article-title":"VDJ recombination","volume":"13","author":"Alt","year":"1992","journal-title":"Immunol. 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