{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:57:35Z","timestamp":1781643455784,"version":"3.54.5"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T00:00:00Z","timestamp":1774051200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universit\u00e4tsklinikum Ulm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Clin Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetic defects in\n                    <jats:italic>IL2RG<\/jats:italic>\n                    or\n                    <jats:italic>JAK3<\/jats:italic>\n                    can cause the phenotype of severe combined immunodeficiency (SCID) with absent T- and non-functional B-lymphocytes (T-B+ SCID). B cell function and the need for immunoglobulin replacement therapy after hematopoietic stem cell transplantation (HSCT) depends on the engraftment of donor B-lymphocytes. In a retrospective study we describe B-lymphocyte reconstitution after HSCT with the aim to identify B cell subpopulations as an early predictor for the maturation and function of B cells after HSCT. All patients included underwent HSCT in a single institution between 1980 and 2017. First, we studied B cell maturation in cryopreserved blood samples of 12 patients with B+ SCID (IL2RG-deficiency) after haploidentical HSCT presenting with mixed B cell chimerism. Recipient and donor B cell subpopulations were identified by HLA-staining using flow cytometry. In a consecutive step we compared B cell subpopulations irrespective of chimerism between patients with or without post-transplant B cell function. Samples for this study were obtained between day\u2009+\u200990 to +\u2009250 after HSCT from 25 post-transplant long-term survivors with B-positive SCID (9 with genetic variants in\n                    <jats:italic>JAK3<\/jats:italic>\n                    , 16 in\n                    <jats:italic>IL2RG)<\/jats:italic>\n                    , 9\/25 were dependent and 16\/25 independent of immunoglobulin (Ig) -substitution.\n                  <\/jats:p>\n                  <jats:p>We demonstrate that a proportion of less than 2% of donor B cells can be sufficient for posttransplant B cell function and that a proportion of more than 4.7% of switched memory (IgM-) B cells in the memory B cell population (CD19\u2009+\u2009CD27+) between days\u2009+\u200990 and +\u2009250 after HSCT correlates with normal B cell function and independence from immunoglobulin substitution.<\/jats:p>","DOI":"10.1007\/s10875-026-02004-2","type":"journal-article","created":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:15:48Z","timestamp":1774070148000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Posttransplant B cell Development and Function in Patients with B cell Positive SCID Caused by Pathogenic Variants in IL2RG and JAK3"],"prefix":"10.1007","volume":"46","author":[{"given":"Eva-Maria","family":"Jacobsen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah","family":"Khazaleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Felgentreff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Furlan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Wustrau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehtap","family":"Sirin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Cario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Pannicke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus-Michael","family":"Debatin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilhelm","family":"Friedrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar S.","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Hoenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,21]]},"reference":[{"issue":"26","key":"2004_CR1","doi-asserted-by":"publisher","first-page":"6824","DOI":"10.1182\/blood-2011-06-362533","volume":"118","author":"M Recher","year":"2011","unstructured":"Recher M, Berglund LJ, Avery DT, et al. IL-21 is the primary common gamma chain-binding cytokine required for human B-cell differentiation in vivo. Blood. 2011;118(26):6824\u201335.","journal-title":"Blood"},{"issue":"1","key":"2004_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4049\/jimmunol.167.1.1","volume":"167","author":"H Asao","year":"2001","unstructured":"Asao H, Okuyama C, Kumaki S, et al. Cutting edge: the common gamma-chain is an indispensable subunit of the IL-21 receptor complex. J Immunol. 2001;167(1):1\u20135.","journal-title":"J Immunol"},{"issue":"26","key":"2004_CR3","doi-asserted-by":"publisher","first-page":"2967","DOI":"10.1182\/blood-2017-10-809822","volume":"131","author":"AM Miggelbrink","year":"2018","unstructured":"Miggelbrink AM, Logan BR, Buckley RH, et al. B-cell differentiation and IL-21 response in IL2RG\/JAK3 SCID patients after hematopoietic stem cell transplantation. Blood. 2018;131(26):2967\u201377.","journal-title":"Blood"},{"issue":"3","key":"2004_CR4","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1002\/1521-4141(200003)30:3<732::AID-IMMU732>3.0.CO;2-L","volume":"30","author":"H White","year":"2000","unstructured":"White H, Thrasher A, Veys P, Kinnon C, Gaspar HB. Intrinsic defects of B cell function in X-linked severe combined immunodeficiency. Eur J Immunol. 2000;30(3):732\u20137.","journal-title":"Eur J Immunol"},{"issue":"3","key":"2004_CR5","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.jaci.2010.06.015","volume":"126","author":"AR Gennery","year":"2010","unstructured":"Gennery AR, Slatter MA, Grandin L, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126(3):602\u2013e610601.","journal-title":"J Allergy Clin Immunol"},{"key":"2004_CR6","doi-asserted-by":"publisher","unstructured":"LankesterAC, Neven B, Mahlaoui N et al. Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006\u20132014 European cohort. J Allergy Clin Immunol. 2022;149(5):1744-54. https:\/\/doi.org\/10.1016\/j.jaci.2021.10.017","DOI":"10.1016\/j.jaci.2021.10.017"},{"key":"2004_CR7","doi-asserted-by":"publisher","unstructured":"Fischer A, Hacein-Bey-Abina S. Gene therapy for severe combined immunodeficiencies and beyond. J Exp Med. 2020;217(2). https:\/\/doi.org\/10.1084\/jem.20190607","DOI":"10.1084\/jem.20190607"},{"issue":"6","key":"2004_CR8","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1111\/cge.12576","volume":"88","author":"A Fischer","year":"2015","unstructured":"Fischer A, Hacein-Bey Abina S, Touzot F, Cavazzana M. Gene therapy for primary immunodeficiencies. Clin Genet. 2015;88(6):507\u201315.","journal-title":"Clin Genet"},{"key":"2004_CR9","doi-asserted-by":"publisher","unstructured":"Martin F, Kearney JF. Marginal-zone B cells. Nat Rev Immunol. 2002;2(5):323\u2009\u2013\u200935. https:\/\/doi.org\/10.1038\/nri799","DOI":"10.1038\/nri799"},{"key":"2004_CR10","doi-asserted-by":"publisher","first-page":"782","DOI":"10.3389\/fimmu.2019.00782","volume":"10","author":"NG van der Maas","year":"2019","unstructured":"van der Maas NG, Berghuis D, van der Burg M, Lankester AC. B Cell Reconstitution and Influencing Factors After Hematopoietic Stem Cell Transplantation in Children. Front Immunol. 2019;10:782. https:\/\/doi.org\/10.3389\/fimmu.2019.00782.","journal-title":"Front Immunol"},{"issue":"3","key":"2004_CR11","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1111\/cei.12915","volume":"188","author":"S Jolles","year":"2017","unstructured":"Jolles S, Chapel H, Litzman J. When to initiate immunoglobulin replacement therapy (IGRT) in antibody deficiency: a practical approach. Clin Exp Immunol. 2017;188(3):333\u201341. https:\/\/doi.org\/10.1111\/cei.12915. e-pub ahead of print 2016\/12\/22.","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"2004_CR12","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.jaip.2024.12.024","volume":"13","author":"IM Otani","year":"2025","unstructured":"Otani IM, Ballow M. If and When to Consider Prophylactic Immunoglobulin Replacement Therapy in Secondary Hypogammaglobulinemia. J Allergy Clin Immunol Pract. 2025;13(3):511\u201321. https:\/\/doi.org\/10.1016\/j.jaip.2024.12.024. e-pub ahead of print 2024\/12\/27.","journal-title":"J Allergy Clin Immunol Pract"}],"container-title":["Journal of Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10875-026-02004-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-026-02004-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10875-026-02004-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:35:55Z","timestamp":1781642155000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10875-026-02004-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,21]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2004"],"URL":"https:\/\/doi.org\/10.1007\/s10875-026-02004-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7329087\/v1","asserted-by":"object"}]},"ISSN":["1573-2592"],"issn-type":[{"value":"1573-2592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,21]]},"assertion":[{"value":"8 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the local Ethics Committee of UlmUniversity (reference\/review number 20122017).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Written informed consent for participation was obtained from all patients and\/or their legal guardians included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"43"}}