Dhenni Rama, Hoppé Alexandra Carey, Reynaldi Arnold, Kyaw Wunna, Handoko Nathalie Tricia, Grootveld Abigail K, Keith Yuki Honda, Bhattacharyya Nayan Deger, Ahel Holly I, Telfser Aiden Josiah, McCorkindale Andrew N, Yazar Seyhan, Bui Christina H T, Smith James T, Khoo Weng Hua, Boyd Mollie, Obeid Solange, Milner Brad, Starr Mitchell, Brilot Fabienne, Milogiannakis Vanessa, Akerman Anouschka, Aggarwal Anupriya, Davenport Miles P, Deenick Elissa K, Chaffer Christine L, Croucher Peter I, Brink Robert, Goldstein Leonard D, Cromer Deborah, Turville Stuart G, Kelleher Anthony D, Venturi Vanessa, Munier C Mee Ling, Phan Tri Giang
Precision Immunology Program, Garvan Institute of Medical Research, Sydney, NSW, Australia; St. Vincent's Healthcare Clinical Campus, School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Kensington, Sydney, NSW, Australia.
Immunovirology and Pathogenesis Program, Kirby Institute, UNSW Sydney, Sydney, NSW, Australia.
Cell. 2025 Jun 26;188(13):3477-3496.e22. doi: 10.1016/j.cell.2025.04.005. Epub 2025 Apr 29.
Vaccines generate long-lived plasma cells and memory B cells (Bmems) that may re-enter secondary germinal centers (GCs) to further mutate their B cell receptor upon boosting and re-exposure to antigen. We show in mouse models that lymph nodes draining the site of primary vaccination harbor a subset of Bmems that reside in the subcapsular niche, generate larger recall responses, and are more likely to re-enter GCs compared with circulating Bmems in non-draining lymph nodes. This location-dependent recall of Bmems into the GC in the draining lymph node was dependent on CD169 subcapsular sinus macrophages (SSMs) in the subcapsular niche. In human participants, boosting of the BNT162b2 vaccine in the same arm generated more rapid secretion of broadly neutralizing antibodies, GC participation, and clonal expansion of SARS-CoV-2-specific B cells than boosting of the opposite arm. These data reveal an unappreciated role for primed draining lymph node SSMs in Bmem cell fate determination.
疫苗可产生长寿浆细胞和记忆B细胞（Bmems），在加强免疫及再次接触抗原时，这些细胞可能重新进入二级生发中心（GCs），进一步使其B细胞受体发生突变。我们在小鼠模型中发现，引流初次接种部位的淋巴结中存在一部分Bmems，它们位于被膜下小生境，能产生更强的回忆反应，与未引流淋巴结中的循环Bmems相比，更有可能重新进入GCs。引流淋巴结中Bmems这种依赖位置的GC召回取决于被膜下小生境中的CD169被膜下窦巨噬细胞（SSMs）。在人类受试者中，同一侧手臂接种BNT162b2疫苗加强免疫比另一侧手臂接种产生更快速的广泛中和抗体分泌、GC参与以及SARS-CoV-2特异性B细胞的克隆扩增。这些数据揭示了初始引流淋巴结SSMs在Bmem细胞命运决定中未被重视的作用。
