Department of Microbiology, Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Department of Biomedical Sciences, Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Front Immunol. 2024 Apr 12;15:1340001. doi: 10.3389/fimmu.2024.1340001. eCollection 2024.
Germinal center (GC) responses are essential for establishing protective, long-lasting immunity through the differentiation of GC B cells (B) and plasma cells (B), along with the generation of antigen-specific antibodies. Among the various pathways influencing immune responses, the STING (Stimulator of Interferon Genes) pathway has emerged as significant, especially in innate immunity, and extends its influence to adaptive responses. In this study, we examined how the STING ligand cGAMP can modulate these key elements of the adaptive immune response, particularly in enhancing GC reactions and the differentiation of B, B, and follicular helper T cells (T). Employing models, we evaluated various antigens and the administration of cGAMP in Alum adjuvant, investigating the differentiation of B, B, and T cells, along with the production of antigen-specific antibodies. cGAMP enhances the differentiation of B and B, leading to increased antigen-specific antibody production. This effect is shown to be type I Interferon-dependent, with a substantial reduction in B frequency upon interferon (IFN)-β blockade. Additionally, cGAMP's influence on T differentiation varies over time, which may be critical for refining vaccine strategies. The findings elucidate a complex, antigen-specific influence of cGAMP on T and B cell responses, providing insights that could optimize vaccine efficacy.
生发中心（GC）反应对于通过 GC B 细胞（B 细胞）和浆细胞（B 细胞）的分化以及产生抗原特异性抗体来建立保护性、持久的免疫至关重要。在影响免疫反应的各种途径中，STING（干扰素基因刺激物）途径已经变得非常重要，特别是在先天免疫中，并将其影响扩展到适应性反应。在这项研究中，我们研究了 STING 配体 cGAMP 如何调节适应性免疫反应的这些关键要素，特别是在增强 GC 反应和 B、B 和滤泡辅助 T 细胞（T）的分化方面。我们使用 模型评估了各种抗原和 cGAMP 在 Alum 佐剂中的给药，研究了 B、B 和 T 细胞的分化以及抗原特异性抗体的产生。cGAMP 增强了 B 和 B 的分化，导致抗原特异性抗体的产生增加。这种效应依赖于 I 型干扰素，IFN-β 阻断后 B 细胞的频率显著降低。此外，cGAMP 对 T 细胞分化的影响随时间而变化，这对于完善疫苗策略可能至关重要。这些发现阐明了 cGAMP 对 T 和 B 细胞反应的复杂、抗原特异性影响，为优化疫苗功效提供了见解。
