Competition propels, rather than limits, the success of low-affinity B cells in the germinal center response

作者：Runhan Li, Keyan Bao, Can Liu, Xue‐Jing Ma, Zhaolin Hua, Ping Zhu, Baidong Hou · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.115334 · 被引用次数：9 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

The germinal center (GC) sets an environment where antigen-specific B cells are compelled to continuously increase their affinity to compete for the antigen and obtain Tfh help for survival and propagation. Previous studies indicated that low-affinity B cells are disadvantaged in the presence of high-affinity ones, suggesting that competition may lead to the elimination of low-affinity B cells and their descendants. However, using a multivalent virus-mimicking antigen, our study demonstrates that low-affinity B cells not only successfully participate in GC responses alongside high-affinity B cells but also undergo accelerated affinity maturation under the more stringent competition. Furthermore, our cryo-electron-microscopy-based structural analysis reveals that both low-affinity and high-affinity B cells compete for the same antigenic epitope. Although the applicability of this idealized GC competition to true pathogen-induced responses remains uncertain, this change in perspective on the role of competition in low-affinity B cell evolution provides valuable insights for vaccine development.