{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:22:54Z","timestamp":1790209374263,"version":"4.1.0"},"reference-count":27,"publisher":"American Society of Hematology","issue":"17","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Common variable immunodeficiency (CVID) is a disease characterized by increased susceptibility to infections, hypogammaglobulinemia, and immune dysregulation. Although CVID is thought to be a disorder of the peripheral B-cell compartment, in 25% of patients, early B-cell development in the bone marrow is impaired. Because poor B-cell reconstitution after hematopoietic stem cell transplantation has been observed, we hypothesized that in some patients the bone marrow environment is not permissive to B-cell development. Studying the differentiation dynamics of bone marrow-derived CD34+ cells into immature B cells in vitro allowed us to distinguish patients with B-cell intrinsic defects and patients with a nonpermissive bone marrow environment. In the former, immature B cells did not develop and in the latter CD34+ cells differentiated into immature cells in vitro, but less efficiently in vivo. In a further group of patients, the uncommitted precursors were unable to support the constant development of B cells in vitro, indicating a possible low frequency or exhaustion of the precursor population. Hematopoietic stem cell transplantation would result in normal B-cell repopulation in case of intrinsic B-cell defect, but in defective B-cell repopulation in a nonpermissive environment. Our study points to the importance of the bone marrow niche in the pathogenesis of CVID.<\/jats:p>","DOI":"10.1182\/blood.2019003855","type":"journal-article","created":{"date-parts":[[2020,3,11]],"date-time":"2020-03-11T02:00:00Z","timestamp":1583892000000},"page":"1452-1457","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":12,"title":["Nonpermissive bone marrow environment impairs early B-cell development in common variable immunodeficiency"],"prefix":"10.1182","volume":"135","author":[{"given":"Arianna","family":"Troilo","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Wehr","sequence":"first","affiliation":[{"name":"Department of Medicine I,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iga","family":"Janowska","sequence":"first","affiliation":[{"name":"Department of 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