@article{200991,
  author = {Julia Merkenschlager and Andrew Pyo and Gabriela Santos and Dennis Schaefer-Babajew and Melissa Cipolla and Harald Hartweger and Alexander Gitlin and Ned Wingreen and Michel Nussenzweig},
  title = {Regulated somatic hypermutation enhances antibody affinity maturation.},
  abstract = {<p>Germinal centres are specialized microenvironments where B cells undergo affinity maturation. B cells expressing antibodies whose affinity is improved by somatic hypermutation are selected for expansion by limiting numbers of T follicular helper cells. Cell division is accompanied by mutation of the immunoglobulin genes, at what is believed to be a fixed rate of around 1 {\texttimes} 10 per base pair per cell division. As mutagenesis is random, the probability of acquiring deleterious mutations outweighs the probability of acquiring affinity-enhancing mutations. This effect might be heightened, and even become counterproductive, in B cells that express high-affinity antibodies and undergo the greatest number of cell divisions. Here we experimentally examine a theoretical model that explains how affinity maturation could be optimized by varying the rate of somatic hypermutation such that cells that express higher-affinity antibodies divide more but mutate less per division. Data obtained from mice immunized with SARS-CoV-2 vaccines\&nbsp;or a model antigen align with the theoretical model and show that cells producing high-affinity antibodies shorten the G0/G1 phases of the cell cycle and reduce their mutation rates. We propose that these mechanisms safeguard high-affinity B cell lineages and enhance the outcomes of antibody affinity maturation.</p>},
  year = {2025},
  journal = {Nature},
  volume = {641},
  pages = {495-502},
  month = {05/2025},
  issn = {1476-4687},
  doi = {10.1038/s41586-025-08728-2},
  language = {eng},
}