Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics

HW King, N Orban, JC Riches, AJ Clear… - Science …, 2021 - science.org
Science immunology, 2021science.org
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 …
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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