In:
Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 8, No. 79 ( 2023-01-27)
Abstract:
The transcription factor interferon regulatory factor 4 (IRF4) is critical for development of the immune system, especially B and T cells. The IRF4 International Consortium identified seven patients from six families with a combined immunodeficiency who harbored a recurrent heterozygous mutation in IRF4, p.T95R. Despite normal levels of IRF4, patients with IRF4T95R and knock-in mice bearing the same point mutation had multiple B cell defects, including impaired differentiation and immunoglobulin secretion. B cells expressing IRF4T95R failed to express genes required for plasma cell differentiation due to altered DNA-binding specificity involving loss of binding to canonical interferon-stimulated response elements and acquired binding at noncanonical sites. This study defines a previously undescribed cause of immunodeficiency driven by an IRF4 mutation leading to distinct changes in its activity. —CO
Type of Medium:
Online Resource
ISSN:
2470-9468
DOI:
10.1126/sciimmunol.ade7953
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2023
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