{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:31:10Z","timestamp":1790418670517,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"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":[[2000,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To establish the underlying cause of hyper-IgM syndrome in one female patient, B cell function was examined in response to CD40- and IL-4-mediated pathways. When CD40-induced functional responses were measured in unfractionated B cells, CD80 up-regulation, de novo C\u03bc-C\u03b3 recombination, and I\u03b3 transcription were all found to be relatively unaffected. However, CD40- and IL-4-mediated CD23 up-regulation and VDJ-C\u03b3 transcription were clearly diminished compared to control cells. IL-4-induced CD23 expression was measurably reduced in the CD20\u2212 population as well. These results suggested that the patient\u2019s defect is positioned downstream of CD40 contact and affects both CD40\u2212 and IL-4 signal transduction pathways. Further analysis of B cell function in CD19+ B cells revealed a clear B cell defect with respect to I\u03b3 and mature VDJ-C\u03b3 transcription and IgG expression. However, under the same conditions I\u03b5 transcription was relatively normal. Partial restoration of B cell function occurred if PBMC or CD19+ B cells were cultured in vitro in the presence of CD154 plus IL-4. Because addition of IL-4 to cocultures containing activated T cells failed to induce B cells to undergo differentiation, the ability of the patient\u2019s B cells to acquire a responsive phenotype correlated with receiving a sustained signal through CD40. These findings support a model in which the patient expresses an intrinsic defect that is manifested in the failure of specific genes to become transcriptionally active in response to either CD154 or IL-4 and results in a functionally unresponsive B cell phenotype.<\/jats:p>","DOI":"10.4049\/jimmunol.164.6.2871","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T16:28:33Z","timestamp":1398184113000},"page":"2871-2880","source":"Crossref","is-referenced-by-count":11,"title":["A Transcriptional Defect Underlies B Lymphocyte Dysfunction in a Patient Diagnosed with Non-X-Linked Hyper-IgM Syndrome"],"prefix":"10.1093","volume":"164","author":[{"given":"Ameesha","family":"Bhushan","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Barnhart","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Shone","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Song","sequence":"additional","affiliation":[{"name":"Harbor General Hospital, University of California at Los Angeles , Torrance, CA 90502"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori R","family":"Covey","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey , Piscataway, NJ 08854"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,3,15]]},"reference":[{"key":"2026020213181760000_R1","first-page":"101","volume-title":"Immunodefic. 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