1162-Predictable Evolution on Antibody Affinity Landscape

This research explores the evolutionary dynamics of antibody development within germinal centers, utilizing a "parallel replay" experiment to track how B cells improve their antigen affinity. By analyzing over one hundred monoclonal reactions, the authors mapped a genotype-phenotype-fitness landscape to determine how predictable outcomes emerge from variable genetic trajectories. The study reveals that while individual phylogenetic trees appear chaotic, the immune system exerts persistent selection to favor higher-affinity mutants despite the frequent production of deleterious mutations. Crucially, the findings suggest that low-affinity B cells found in these centers are recent mutants rather than evidence of a permissive selection process. Furthermore, the researchers identified that survivorship biases often distort our perception of evolutionary history, making affinity gains appear to plateau prematurely. Ultimately, the work demonstrates that affinity maturation is a robust but constrained process driven by the interplay of somatic hypermutation and competitive selection.References:DeWitt WS, Vora AA, Araki T, Galloway JG, Alkutkar T, Bortolatto J, Castro TBR, Dumm W, Jennings-Shaffer C, Jia T, Mesin L, Ozorowski G, Pae J, Ralph DK, Bloom JD, Nourmohammad A, Song YS, Ward AB, Starr TN, Matsen FA 4th, Victora GD. Replaying germinal center evolution on a quantified affinity landscape. Cell. 2026 Jun 5:S0092-8674(26)00572-6. doi: 10.1016/j.cell.2026.05.013. Epub ahead of print. PMID: 42248140.前往小宇宙评论区与主播互动