| First Author | Mlynarczyk C | Year | 2023 |
| Journal | Science | Volume | 379 |
| Issue | 6629 | Pages | eabj7412 |
| PubMed ID | 36656933 | Mgi Jnum | J:332796 |
| Mgi Id | MGI:7428838 | Doi | 10.1126/science.abj7412 |
| Citation | Mlynarczyk C, et al. (2023) BTG1 mutation yields supercompetitive B cells primed for malignant transformation. Science 379(6629):eabj7412 |
| abstractText | 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 BTG1 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. |
