Tissue-directed maintenance of vaccine-specific human B-cell memory

Описание: 2026 Immcantation Users Group Meeting https://immcantation.github.io/users-...
Title: Tissue-directed maintenance of vaccine-specific human B-cell memory
Speaker: Eric Zhang, Columbia University Irving Medical Center (US)
Abstract:
The formation and maintenance of memory B cells (MBCs) after vaccination and infection is essential for lifelong immunity. A minority of MBCs circulate; instead, most reside in lymphoid reservoirs such as the spleen, lymph nodes, and bone marrow. In humans, it remains unclear whether these compartments maintain distinct MBC subsets and if such subsets contribute to vaccine immunity. To address this, we performed paired single-cell RNA and B-cell receptor (BCR) sequencing of four ubiquitous antigen-specific MBC populations—measles and tetanus (childhood-primed) and SARS-CoV-2 and H1N1 influenza (recently primed/boosted)—across spleen, lymph nodes, and bone marrow. We identified three major subsets enriched in distinct tissues: classical MBCs in lymph nodes, marginal zone–like MBCs in spleen, and atypical MBCs in bone marrow. All three subsets were present in each antigen-specific population, but their relative proportions were shaped by both tissue and antigen. Using the Immcantation framework, we found that antigen-specific MBCs were variably clonally expanded, with individual clones spanning all three subsets in a tissue-guided manner. Additionally, each subset was represented amongst class-switched and non-class-switched BCRs. Mutational inference and phylogenetic analysis revealed that MBCs sharing identical BCRs often adopted different subset identities, indicating that MBC cellular identity is highly dynamic and uncoupled from lineage. Together, these findings demonstrate substantial phenotypic and functional heterogeneity in the tissue reservoirs of human memory B cells, with implications for future vaccine design and delivery.