{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T21:16:04Z","timestamp":1786828564838,"version":"build-2736575974"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2010,6,1]],"date-time":"2010-06-01T00:00:00Z","timestamp":1275350400000},"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":[[2010,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Several lines of evidence have demonstrated B cell intrinsic activation defects in patients with common variable immunodeficiency (CVID). The rapid increase of intracellular free calcium concentrations after engagement of the BCR represents one crucial element in this activation process. The analysis of 53 patients with CVID for BCR-induced calcium flux identified a subgroup of patients with significantly reduced Ca2+ signals in primary B cells. This subgroup strongly corresponded to the class Ia of the Freiburg classification. Comparison at the level of defined B cell subpopulations revealed reduced Ca2+ signals in all mature B cell populations of patients with CVID class Ia when compared with healthy individuals and other groups of patients with CVID but not in circulating transitional B cells. BCR-induced Ca2+ responses were the lowest in CD21low B cells in patients as well as healthy donors, indicating an additional cell-specific mechanism inhibiting the Ca2+ flux. Although proximal BCR signaling events are unperturbed in patients\u2019 B cells, including normal phospholipase C\u03b32 phosphorylation and Ca2+ release from intracellular stores, Ca2+ influx from the extracellular space is significantly impaired. CD22, a negative regulator of calcium signals in B cells, is highly expressed on CD21low B cells from patients with CVID Ia and might be involved in the attenuated Ca2+ response of this B cell subpopulation. These data from patients with CVID suggest that a defect leading to impaired BCR-induced calcium signaling is associated with the expansion of CD21low B cells, hypogammaglobulinemia, autoimmune dysregulation, and lymphadenopathy.<\/jats:p>","DOI":"10.4049\/jimmunol.1000434","type":"journal-article","created":{"date-parts":[[2010,5,21]],"date-time":"2010-05-21T21:11:10Z","timestamp":1274476270000},"page":"7305-7313","source":"Crossref","is-referenced-by-count":69,"title":["B Cell Receptor-Mediated Calcium Signaling Is Impaired in B Lymphocytes of Type Ia Patients with Common Variable Immunodeficiency"],"prefix":"10.1093","volume":"184","author":[{"given":"Christian","family":"Foerster","sequence":"first","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Voelxen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirzokhid","family":"Rakhmanov","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Gutenberger","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigune","family":"Goldacker","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Thiel","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Feske","sequence":"additional","affiliation":[{"name":"Langone Medical Center, New York University , New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Hartmut","family":"Peter","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[{"name":"Division of Rheumatology and Clinical Immunology, Centre of Chronic Immunodeficiency, University Medical Centre , Freiburg,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,6,15]]},"reference":[{"key":"2026012806354590600_r1","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.jaci.2009.10.013","article-title":"Primary immunodeficiencies: 2009 update.","volume":"124","author":"Notarangelo","year":"2009","journal-title":"J. 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