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

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 thi..