دورية أكاديمية
أعرض في EDS

An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway.

التفاصيل البيبلوغرافية
العنوان: An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway.
المؤلفون: Trezise S; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Harvard University, Boston, MA, United States., Kong IY; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Weill Cornell Medicine, New York, NY, United States., Hawkins ED; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Herold MJ; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Willis SN; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia., Nutt SL; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.; Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia.
المصدر: Frontiers in immunology [Front Immunol] 2023 Feb 13; Vol. 14, pp. 1089243. Date of Electronic Publication: 2023 Feb 13 (Print Publication: 2023).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Endoplasmic Reticulum-Associated Degradation* , Secretory Pathway*, Antibodies ; B-Lymphocytes ; Immunity, Humoral
مستخلص: Background: Humoral immunity depends on the differentiation of B cells into antibody secreting cells (ASCs). Excess or inappropriate ASC differentiation can lead to antibody-mediated autoimmune diseases, while impaired differentiation results in immunodeficiency.
Methods: We have used CRISPR/Cas9 technology in primary B cells to screen for regulators of terminal differentiation and antibody production.
Results: We identified several new positive ( Sec61a1 , Hspa5 ) and negative ( Arhgef18 , Pold1 , Pax5 , Ets1 ) regulators that impacted on the differentiation process. Other genes limited the proliferative capacity of activated B cells ( Sumo2 , Vcp , Selk ). The largest number of genes identified in this screen (35) were required for antibody secretion. These included genes involved in endoplasmic reticulum-associated degradation and the unfolded protein response, as well as post-translational protein modifications.
Discussion: The genes identified in this study represent weak links in the antibody-secretion pathway that are potential drug targets for antibody-mediated diseases, as well as candidates for genes whose mutation results in primary immune deficiency.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Trezise, Kong, Hawkins, Herold, Willis and Nutt.)
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فهرسة مساهمة: Keywords: ER associated degradation (ERAD); endoplasmic reticulum; humoral immunity; immunodeficiency; in vitro differentiation; plasma cell; unfolded protein response
المشرفين على المادة: 0 (Antibodies)
تواريخ الأحداث: Date Created: 20230302 Date Completed: 20230303 Latest Revision: 20230307
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9969136
DOI: 10.3389/fimmu.2023.1089243
PMID: 36860866
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-3224
DOI:10.3389/fimmu.2023.1089243