Immunization or microbial infection can establish long-term B cell memory not only systemically but also locally. Evidence has suggested that local B cell memory contributes to early local plasmacytic responses after secondary challenge. However, it is unclear whether locality of immunization plays any role in memory B cell participation in recall germinal centers (GCs), which is essential for updating their B cell antigen receptors (BCRs). Using single B cell culture and fate mapping, we have characterized BCR repertoires in recall GCs after boost immunizations at sites local or distal to the priming. Local boosts with homologous antigen recruit the progeny of primary GC B cells to recall GCs more efficiently than do distal boosts. Recall GCs elicited by local boosts contain significantly more B cells with elevated levels of immunoglobulin (Ig) mutation and higher avidity BCRs. This local preference is unaffected by blocking CD40:CD154 interaction to terminate active, GC responses. Local boosts with heterologous antigens elicit secondary GCs with B cell populations enriched for cross-reactivity to the prime and boost antigens; in contrast, cross-reactive GC B cells are rare after distal boosts. Our results suggest that local B cell memory is retained in the form of memory B cells, GC B cells, and GC phenotype B cells that are independent of organized GC structures and that these persistent “primed B cells” contribute to recall GC responses at local sites. Our findings indicate the importance of locality in humoral immunity and inform serial vaccination strategies for evolving viruses.

中文翻译：

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B 细胞记忆的回忆取决于初免和加强免疫的相对位置

免疫或微生物感染不仅可以在全身而且在局部建立长期的B细胞记忆。有证据表明，局部 B 细胞记忆有助于二次攻击后的早期局部浆细胞反应。然而，尚不清楚免疫局部性是否在记忆 B 细胞参与回忆生发中心 (GC) 中发挥任何作用，这对于更新其 B 细胞抗原受体 (BCR) 至关重要。使用单 B 细胞培养和命运图谱，我们在启动局部或远端的加强免疫后，对回忆 GC 中的 BCR 库进行了表征。使用同源抗原的局部加强比远端加强更有效地募集原代 GC B 细胞的后代来召回 GC。回想一下，局部加强引起的 GC 含有明显更多的 B 细胞，其免疫球蛋白 (Ig) 突变水平升高，并且 BCR 亲合力更高。这种局部偏好不受阻断 CD40:CD154 相互作用以终止主动 GC 响应的影响。使用异源抗原进行局部加强，可引发二次 GC，其中 B 细胞群富集，可与初免和加强抗原发生交叉反应；相反，远端加强后交叉反应的 GC B 细胞很少见。我们的结果表明，局部 B 细胞记忆以记忆 B 细胞、GC B 细胞和 GC 表型 B 细胞的形式保留，这些细胞独立于有组织的 GC 结构，并且这些持久的“启动 B 细胞”有助于回忆局部的 GC 反应。网站。我们的研究结果表明了局部性在体液免疫中的重要性，并为进化病毒的连续疫苗接种策略提供了信息。