Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC.
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC
J Immunol. 2021 Oct 15;207(8):1978-1989. doi: 10.4049/jimmunol.2100336. Epub 2021 Sep 17.
The inability of T cell-independent type 2 (TI-2) Ags to induce recall responses is a poorly understood facet of humoral immunity, yet critically important for improving vaccines. Using normal and VB1-8 transgenic mice, we demonstrate that B cell-intrinsic PD-1 expression negatively regulates TI-2 memory B cell (B) generation and reactivation in part through interacting with PDL1 and PDL2 on non-Ag-specific cells. We also identified a significant role for PDL2 expression on B in inhibiting reactivation and Ab production, thereby revealing a novel self-regulatory mechanism exists for TI-2 B This regulation impacts responses to clinically relevant vaccines, because PD-1 deficiency was associated with significantly increased Ab boosting to the pneumococcal vaccine after both vaccination and infection. Notably, we found a B cell-activating adjuvant enabled even greater boosting of protective pneumococcal polysaccharide-specific IgG responses when PD-1 inhibition was relieved. This work highlights unique self-regulation by TI-2 B and reveals new opportunities for significantly improving TI-2 Ag-based vaccine responses.
T 细胞非依赖型 2 型（TI-2）抗原无法诱导回忆反应，这是体液免疫中一个尚未被充分理解的方面，但对于改进疫苗至关重要。使用正常和 VB1-8 转基因小鼠，我们证明了 B 细胞内在 PD-1 的表达通过与非抗原特异性细胞上的 PDL1 和 PDL2 相互作用，负调节 TI-2 记忆 B 细胞（B）的产生和再激活。我们还发现 PDL2 在 B 细胞上的表达在抑制再激活和 Ab 产生方面起着重要作用，从而揭示了 TI-2 B 存在一种新的自我调节机制。这种调节会影响到临床相关疫苗的反应，因为 PD-1 缺陷与肺炎球菌疫苗接种和感染后对肺炎球菌疫苗的 Ab 增强显著相关。值得注意的是，我们发现 B 细胞激活佐剂在缓解 PD-1 抑制时，甚至可以更有效地增强对保护性肺炎球菌多糖特异性 IgG 反应的增强。这项工作突出了 TI-2 B 的独特自我调节，并为显著改善 TI-2 Ag 为基础的疫苗反应提供了新的机会。
