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A human B cell roadmap
B cells undergo affinity maturation and class switch recombination (CSR) within germinal centers (GCs) to facilitate protective antibody responses against pathogens. King et al. performed single-cell transcriptome and antibody repertoire profiling of human tonsils to examine how antibody-based selection affects B cell maturation within GCs. In addition to generating a detailed resource of transcriptional programs associated with antibody class, they identified a pre-GC B cell state that expressed unmutated IgM and IgD but was enriched for CSR-associated genes and germline transcripts. These results indicate that a subset of B cells may be primed for CSR before GC entry and highlight antibody repertoire dynamics during B cell fate decisions in secondary lymphoid organs.
Abstract
Protective humoral memory forms in secondary lymphoid organs where B cells undergo affinity maturation and differentiation into memory or plasma cells. Here, we provide a comprehensive roadmap of human B cell maturation with single-cell transcriptomics matched with bulk and single-cell antibody repertoires to define gene expression, antibody repertoires, and clonal sharing of B cell states at single-cell resolution, including memory B cell heterogeneity that reflects diverse functional and signaling states. We reconstruct gene expression dynamics during B cell activation to reveal a pre–germinal center state primed to undergo class switch recombination and dissect how antibody class–dependent gene expression in germinal center and memory B cells is linked with a distinct transcriptional wiring with potential to influence their fate and function. Our analyses reveal the dynamic cellular states that shape human B cell–mediated immunity and highlight how antibody isotype may play a role during their antibody-based selection.
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