期刊
SCIENCE
卷 379, 期 6629, 页码 252-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abj7412
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Multicellular life relies on altruistic cooperation among cells. However, a study found that mutations in the BTG1 gene disrupt a crucial mechanism that limits B cell fitness during antibody affinity maturation, leading to the emergence of aggressive lymphomas.
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.
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