PT  - JOURNAL ARTICLE
AU  - King, Hamish W.
AU  - Orban, Nara
AU  - Riches, John C.
AU  - Clear, Andrew J.
AU  - Warnes, Gary
AU  - Teichmann, Sarah A.
AU  - James, Louisa K.
TI  - Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics
AID  - 10.1126/sciimmunol.abe6291
DP  - 2021 Feb 12
TA  - Science Immunology
PG  - eabe6291
VI  - 6
IP  - 56
4099  - http://immunology.sciencemag.org/content/6/56/eabe6291.short
4100  - http://immunology.sciencemag.org/content/6/56/eabe6291.full
SO  - Sci. Immunol.2021 Feb 12; 6
AB  - 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.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.