Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Renal Division, Department of Health Sciences, Università degli Studi di Milano, Milano, Italy.
Cell Rep. 2022 Feb 22;38(8):110399. doi: 10.1016/j.celrep.2022.110399. Epub 2022 Feb 1.
Follicular helper T (Tfh) cells promote, whereas follicular regulatory T (Tfr) cells restrain, germinal center (GC) reactions. However, the precise roles of these cells in the complex GC reaction remain poorly understood. Here, we perturb Tfh or Tfr cells after SARS-CoV-2 spike protein vaccination in mice. We find that Tfh cells promote the frequency and somatic hypermutation (SHM) of Spike-specific GC B cells and regulate clonal diversity. Tfr cells similarly control SHM and clonal diversity in the GC but do so by limiting clonal competition. In addition, deletion of Tfh or Tfr cells during primary vaccination results in changes in SHM after vaccine boosting. Aged mice, which have altered Tfh and Tfr cells, have lower GC responses, presenting a bimodal distribution of SHM. Together, these data demonstrate that GC responses to SARS-CoV-2 spike protein vaccines require a fine balance of positive and negative follicular T cell help to optimize humoral immunity.
滤泡辅助 T（Tfh）细胞促进，而滤泡调节 T（Tfr）细胞抑制生发中心（GC）反应。然而，这些细胞在复杂的 GC 反应中的精确作用仍知之甚少。在这里，我们在 SARS-CoV-2 刺突蛋白疫苗接种后对小鼠中的 Tfh 或 Tfr 细胞进行了干扰。我们发现 Tfh 细胞促进了 Spike 特异性 GC B 细胞的频率和体细胞高频突变（SHM），并调节了克隆多样性。Tfr 细胞在 GC 中同样控制着 SHM 和克隆多样性，但通过限制克隆竞争来实现。此外，在初次接种期间删除 Tfh 或 Tfr 细胞会导致疫苗加强后 SHM 的变化。衰老的小鼠，其 Tfh 和 Tfr 细胞发生改变，GC 反应较低，呈现出 SHM 的双峰分布。总之，这些数据表明，对 SARS-CoV-2 刺突蛋白疫苗的 GC 反应需要正性和负性滤泡 T 细胞辅助的精细平衡，以优化体液免疫。
