{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:40:46Z","timestamp":1780641646295,"version":"3.54.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Primary immunodeficiencies consist to a large extent of B cell defects, as indicated by inadequate Ab levels or response upon immunization. Many B cell defects have not yet been well characterized. Our objective was to create reliable in vivo and in vitro assays to routinely analyze human B cell differentiation, proliferation, and Ig production and to define reference ranges for different age categories. The in vitro assays were applied to classify the developmental and\/or functional B cell defects in patients previously diagnosed with common variable immunodeficiency. Apart from standard immunophenotyping of circulating human B cell subsets, an in vitro CFSE dilution assay was used for the assessment of proliferative capacity comparing T cell\u2013dependent and T cell\u2013independent B cell activation. Plasmablast\/plasma cell differentiation was assessed by staining for CD20, CD38, and CD138, and measurement of in vitro Ig secretion. At young age, B cells proliferate upon in vitro activation, but neither differentiate nor produce IgG. These latter functions reached adult levels at 5 and 10 y of age for T cell\u2013dependent versus T cell\u2013independent stimulations, respectively. The capacity of B cells to differentiate into plasmablasts and to produce IgG appeared to be contained within the switched memory B cell pool. Using these assays, we could categorize common variable immunodeficiency patients into subgroups and identified a class-switch recombination defect caused by an UNG mutation in one of the patients. We defined age-related reference ranges for human B cell differentiation. Our findings indicate that in vivo B cell functionality can be tested in vitro and helps to diagnose suspected B cell defects.<\/jats:p>","DOI":"10.4049\/jimmunol.1201807","type":"journal-article","created":{"date-parts":[[2013,4,13]],"date-time":"2013-04-13T03:37:07Z","timestamp":1365824227000},"page":"5012-5019","source":"Crossref","is-referenced-by-count":29,"title":["Identification of B Cell Defects Using Age-Defined Reference Ranges for In Vivo and In Vitro B Cell Differentiation"],"prefix":"10.1093","volume":"190","author":[{"given":"Daan J","family":"aan de Kerk","sequence":"first","affiliation":[{"name":"Department of Pediatric Hematology, Immunology, and Infectious Diseases, Emma Children\u2019s Hospital, Academic Medical Center , 1105 AZ Amsterdam,","place":["The Netherlands"]},{"name":"Department of Experimental Immunology, Academic Medical Center , 1105 AZ Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiel H","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Immunology, and Infectious Diseases, Emma Children\u2019s Hospital, Academic Medical Center , 1105 AZ Amsterdam,","place":["The Netherlands"]},{"name":"Department of Experimental Immunology, Academic Medical Center , 1105 AZ Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ineke J M","family":"ten Berge","sequence":"additional","affiliation":[{"name":"Renal Transplant Unit, Department of Nephrology, Division of Internal Medicine, Academic Medical Centre , 1105 AZ Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester M M","family":"van Leeuwen","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology, Academic Medical Center , 1105 AZ Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taco W","family":"Kuijpers","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Immunology, and Infectious Diseases, Emma Children\u2019s Hospital, Academic Medical Center , 1105 AZ Amsterdam,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,5,15]]},"reference":[{"key":"2025032406593942600_r1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/S1525-1578(10)60493-X","article-title":"The molecular pathology of primary immunodeficiencies","volume":"6","author":"Lim","year":"2004","journal-title":"J. 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