Browsing by Author "Schickel, Jean Nicolas"

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    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.