2025-03-19 ロックフェラー大学
<関連情報>
- https://www.rockefeller.edu/news/37504-new-understanding-of-b-cell-mutation-strategies-could-have-implications-for-vaccines/
- https://www.nature.com/articles/s41586-025-08728-2
制御された体細胞超変異が抗体親和性の成熟を促進する Regulated somatic hypermutation enhances antibody affinity maturation
Julia Merkenschlager,Andrew G. T. Pyo,Gabriela S. Silva Santos,Dennis Schaefer-Babajew,Melissa Cipolla,Harald Hartweger,Alexander D. Gitlin,Ned S. Wingreen & Michel C. Nussenzweig
Nature Published:19 March 2025
DOI:https://doi.org/10.1038/s41586-025-08728-2
Abstract
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 × 10-3 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 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.
