BTG1 mutation yields supercompetitive B cells primed for malignant transformation Journal Article
| Authors: | Mlynarczyk, C.; Teater, M.; Pae, J.; Chin, C. R.; Wang, L.; Arulraj, T.; Barisic, D.; Papin, A.; Hoehn, K. B.; Kots, E.; Ersching, J.; Bandyopadhyay, A.; Barin, E.; Poh, H. X.; Evans, C. M.; Chadburn, A.; Chen, Z.; Shen, H.; Isles, H. M.; Pelzer, B.; Tsialta, I.; Doane, A. S.; Geng, H.; Rehman, M. H.; Melnick, J.; Morgan, W.; Nguyen, D. T. T.; Elemento, O.; Kharas, M. G.; Jaffrey, S. R.; Scott, D. W.; Khelashvili, G.; Meyer-Hermann, M.; Victora, G. D.; Melnick, A. |
| Article Title: | BTG1 mutation yields supercompetitive B cells primed for malignant transformation |
| Abstract: | 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. © 2023 the authors, some rights reserved; exclusive licensee. |
| Keywords: | genetics; mutation; mouse; animal; animals; mice; immune system; neoplasm proteins; protein; b lymphocyte; b-lymphocytes; germinal center; tumor protein; lymphoma; fitness; immunity; antibody; antibody affinity; biotransformation; cell; natural selection; humans; human; btg1 protein, human; btg1 protein, mouse |
| Journal Title: | Science |
| Volume: | 379 |
| Issue: | 6629 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2023-01-20 |
| Start Page: | eabj7412 |
| Language: | English |
| DOI: | 10.1126/science.abj7412 |
| PUBMED: | 36656933 |
| PROVIDER: | scopus |
| PMCID: | PMC10515739 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2023 -- Source: Scopus |
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