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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
Science (American Association for the Advancement of Science), 01/2023, Letnik: 379, Številka: 6629Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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