An arrayed CRISPR screen of primary B cells reveals the essential elements of the antibody secretion pathway
- Author(s)
- Trezise, S; Kong, IY; Hawkins, ED; Herold, MJ; Willis, SN; Nutt, SL;
- Journal Title
- Frontiers in Immunology
- Abstract
- 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.
- Publisher
- Frontiers Media
- Keywords
- Endoplasmic Reticulum-Associated Degradation; Secretory Pathway; Antibodies; B-Lymphocytes; Immunity, Humoral; ER associated degradation (ERAD); endoplasmic reticulum; humoral immunity; immunodeficiency; in vitro differentiation; plasma cell; unfolded protein response
- Research Division(s)
- Immunology; Blood Cells And Blood Cancer; Inflammation
- PubMed ID
- 36860866
- Publisher's Version
- https://doi.org/10.3389/fimmu.2023.1089243
- Open Access at Publisher's Site
https://doi.org/10.3389/fimmu.2023.1089243- Terms of Use/Rights Notice
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Creation Date: 2023-03-08 03:16:08
Last Modified: 2023-03-08 04:07:58