{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:27:25Z","timestamp":1791289645122,"version":"4.3.0"},"reference-count":38,"publisher":"Rockefeller University Press","issue":"12","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,11,19]]},"abstract":"<jats:p>Nuclear factor-\u03baB (NF-\u03baB) controls genes involved in normal lymphocyte functions, but constitutive NF-\u03baB activation is often associated with B cell malignancy. Using high-throughput whole transcriptome sequencing, we investigated a unique family with hereditary polyclonal B cell lymphocytosis. We found a novel germline heterozygous missense mutation (E127G) in affected patients in the gene encoding CARD11, a scaffolding protein required for antigen receptor (AgR)\u2013induced NF-\u03baB activation in both B and T lymphocytes. We subsequently identified a second germline mutation (G116S) in an unrelated, phenotypically similar patient, confirming mutations in CARD11 drive disease. Like somatic, gain-of-function CARD11 mutations described in B cell lymphoma, these germline CARD11 mutants spontaneously aggregate and drive constitutive NF-\u03baB activation. However, these CARD11 mutants rendered patient T cells less responsive to AgR-induced activation. By reexamining this rare genetic disorder first reported four decades ago, our findings provide new insight into why activating CARD11 mutations may induce B cell expansion and preferentially predispose to B cell malignancy without dramatically perturbing T cell homeostasis.<\/jats:p>","DOI":"10.1084\/jem.20120831","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T05:15:07Z","timestamp":1352178907000},"page":"2247-2261","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":190,"title":["Congenital B cell lymphocytosis explained by novel germline <i>CARD11<\/i> mutations"],"prefix":"10.1084","volume":"209","author":[{"given":"Andrew L.","family":"Snow","sequence":"first","affiliation":[{"name":"Lymphocyte Molecular Genetics Unit, Laboratory of Immunology 1 ; 2 ; and 3"},{"name":"Immunopathogenesis Section, Laboratory of Immunoregulation 1 ; 2 ; and 3"},{"name":"Laboratory of Host Defenses; National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Bethesda, MD 20892 1 ; 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