Studying immune cell fate inside the body of mice with CRISPR

Plasma cells are the immune system’s antibody factories, but how B cells make the switch to become plasma cells has remained unclear. By developing a new in vivo CRISPR screening strategy, researchers from the lab of Meinrad Busslinger at the IMP identified dozens of previously unknown genes that drive this transition. Their findings are published in the Journal of Experimental Medicine.

A 3D illustration of a plasma cell (purple) releasing antibodies (white, yellow), the key molecules that target pathogens during an immune response.

Lesly Calderón, a senior researcher from the lab of Meinrad Busslinger at the IMP, has collaborated with the lab of Johannes Zuber to develop a new way to systematically identify genes that regulate plasma cell formation directly inside living mice. By combining CRISPR/Cas9 gene editing with an innovative in vivo screening strategy, the team discovered dozens of previously unknown genes that control the switch from B cells to plasma cells—revealing how the immune system makes these critical cell fate decisions in its natural environment, and introducing a powerful and broadly applicable in vivo screening strategy.

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Original Publication

L. Calderón, M. Schäfer, M. Rončević, R. Rauschmeier, M. Jaritz, T. A. Schwickert, Q. Sun, A. Pauli, J. Zuber & M. Busslinger “In vivo CRISPR/Cas9 screens identify new regulators of B cell activation and plasma cell differentiation.” Journal of Experimental Medicine (2026). DOI: 10.1084/jem.20250594

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