Browsing by Author "Walter, Jolan E."

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Publication
    Activation-induced cytidine deaminase (AID) is required for B-cell tolerance in humans
    (Natl Acad Sciences, 2011-07-12) Meyers, Greta; Ng, Yen-Shing; Bannock, Jason M.; Lavoie, Aubert; Walter, Jolan E.; Notarangelo, Luigi D.; Kılıç, Sara S.; Aksu, Guzide; Debre, Marianne; Rieux-Laucat, Frederic; Conley, Mary Ellen; Cunningham-Rundles, Charlotte; Durandy, Anne; Meffre, Eric; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; AAH-1658-2021
    Impaired immune functions leading to primary immunodeficiencies often correlate with paradoxical autoimmune complications; patients with hyper-IgM syndromes who are deficient in activation-induced cytidine deaminase (AID), which is required for classs-witch recombination and somatic hypermutation, are prone to develop autoimmune diseases. To investigate the impact of AID-deficiency on early B-cell tolerance checkpoints in humans, we tested by ELISA the reactivity of recombinant antibodies isolated from single B cells from AID-deficient patients. New emigrant/transitional and mature naive B cells from AID-deficient patients express an abnormal Ig repertoire and high frequencies of autoreactive antibodies, demonstrating that AID is required for the establishment of both central and peripheral B-cell tolerance. In addition, B-cell tolerance was further breached in AID-deficient patients as illustrated by the detection of anti-nuclear IgM antibodies in the serum of all patients. Thus, we identified a major and previously unsuspected role for AID in the removal of developing autoreactive B cells in humans.
  • Thumbnail Image
    Item
    Activation-induced cytidine deaminase expression in human b cell precursors ıs essential for central b cell tolerance
    (Cell Press, 2015-11-17) Cantaert, Tineke; Schickel, Jean Nicolas; Bannock, Jason M.; Ng, Yen Shing; Massad, Christopher; Oe, Tyler; Wu, Renee; Lavoie, Aubert; Walter, Jolan E.; Notarangelo, Luigi D.; Herz, Waleed Al; Ochs, Hans D.; Nonoyama, Shigeaki; Durandy, Anne; Meffre, Eric; Kılıç, Sara Şebnem; Uludağ Üniversitesi/Tıp Fakültesi/Çocuk Sağlığı ve Hastalıkları Anabilim Dalı.; AAH-1658-2021; 0000-0001-8571-2581; 34975059200
    Activation-induced cytidine deaminase (AID), the enzyme- mediating class-switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes, is essential for the removal of developing autoreactive B cells. How AID mediates central B cell tolerance remains unknown. We report that AID enzymes were produced in a discrete population of immature B cells that expressed recombination-activating gene 2 (RAG2), suggesting that they undergo secondary recombination to edit autoreactive antibodies. However, most AID(+) immature B cells lacked anti-apoptotic MCL-1 and were deleted by apoptosis. AID inhibition using lentiviral-encoded short hairpin (sh)RNA in B cells developing in humanized mice resulted in a failure to remove autoreactive clones. Hence, B cell intrinsic AID expression mediates central B cell tolerance potentially through its RAG-coupled genotoxic activity in self-reactive immature B cells.