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Opinions vary on which affected patients should receive a CVID diagnosis which\u00a0confuses clinicians and erects reproducibility barriers for researchers. Most experts agree that CVID's most indeliable feature is defective germinal center (GC) production of isotype\u2010switched, affinity\u2010maturated antibodies. Here, we review the biological factors contributing to CVID\u2010associated GC dysfunction including genetic, epigenetic, tolerogenic, microbiome, and regulatory abnormalities. We also discuss the consequences of these biological phenomena to the development of non\u2010infectious disease complications. Finally, we opine on topics and lines of investigation we think hold promise for expanding our mechanistic understanding of this protean condition and for improving the lives of affected patients.<\/jats:p>","DOI":"10.1111\/imr.13291","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T14:00:53Z","timestamp":1701180053000},"page":"233-243","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Common variable immunodeficiency, cross currents, and prevailing winds"],"prefix":"10.1111","volume":"322","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1881-5318","authenticated-orcid":false,"given":"Neil","family":"Romberg","sequence":"first","affiliation":[{"name":"Division of Immunology and Allergy Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Institute for Immunology, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Le\u00a0Coz","sequence":"additional","affiliation":[{"name":"Infinity, Toulouse Institute for Infectious and Inflammatory Diseases University of Toulouse, CNRS, Inserm  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"issue":"3","key":"e_1_2_10_2_1","first-page":"302","article-title":"Arne Tiselius\u2014father of electrophoresis","volume":"80","author":"Kyle RA","year":"2005","journal-title":"Mayo Clin 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