A CRISPR screen in living mice maps the hidden regulators of antibody factories
Researchers have developed a novel in vivo CRISPR/Cas9 screening system to identify genes that control B cell activation and their differentiation into antibody-producing plasma cells. Using genetically modified mice with enhanced susceptibility to viral infection in B cells, the team screened 379 guide RNAs targeting genes highly expressed in plasma cells. The screen, conducted in immunized animals, pinpointed 41 novel regulators—23 positive and 18 negative—involved in processes like cell adhesion, signal transduction, and iron transport, revealing a complex genetic network that governs the humoral immune response within the authentic microenvironment of the spleen.
Why it might matter to you:
This work provides a powerful functional genomics map of B cell immunity, directly relevant to vaccine adjuvant research and understanding immune evasion mechanisms. The identified regulators represent new potential targets for modulating antibody responses, which could inform strategies for improving vaccine efficacy or treating antibody-mediated diseases. The in vivo screening methodology itself is a significant advance for probing host-pathogen interactions and immune cell fate decisions in a physiologically relevant context.
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