Details

Autor(en) / Beteiligte

• Mlynarczyk, Coraline
• Teater, Matt
• Pae, Juhee
• Chin, Christopher R
• Wang, Ling
• Arulraj, Theinmozhi
• Barisic, Darko
• Papin, Antonin
• Hoehn, Kenneth B
• Kots, Ekaterina
• Ersching, Jonatan
• Bandyopadhyay, Arnab
• Barin, Ersilia
• Poh, Hui Xian
• Evans, Chiara M
• Chadburn, Amy
• Chen, Zhengming
• Shen, Hao
• Isles, Hannah M
• Pelzer, Benedikt
• Tsialta, Ioanna
• Doane, Ashley S
• Geng, Huimin
• Rehman, Muhammad Hassan
• Melnick, Jonah
• Morgan, Wyatt
• Nguyen, Diu T T
• Elemento, Olivier
• Kharas, Michael G
• Jaffrey, Samie R
• Scott, David W
• Khelashvili, George
• Meyer-Hermann, Michael
• Victora, Gabriel D
• Melnick, Ari

Titel

BTG1 mutation yields supercompetitive B cells primed for malignant transformation

Ist Teil von

• Science (American Association for the Advancement of Science), 2023-01, Vol.379 (6629), p.eabj7412

Ort / Verlag

United States: The American Association for the Advancement of Science

Erscheinungsjahr

2023

Quelle

Science Online_科学在线

Beschreibungen/Notizen

• Multicellular life requires altruistic cooperation between cells. The adaptive immune system is a notable exception, wherein germinal center B cells compete vigorously for limiting positive selection signals. Studying primary human lymphomas and developing new mouse models, we found that mutations affecting disrupt a critical immune gatekeeper mechanism that strictly limits B cell fitness during antibody affinity maturation. This mechanism converted germinal center B cells into supercompetitors that rapidly outstrip their normal counterparts. This effect was conferred by a small shift in MYC protein induction kinetics but resulted in aggressive invasive lymphomas, which in humans are linked to dire clinical outcomes. Our findings reveal a delicate evolutionary trade-off between natural selection of B cells to provide immunity and potentially dangerous features that recall the more competitive nature of unicellular organisms.