RT Journal Article
SR Electronic
T1 Single-cell analysis of human B cell maturation predicts how antibody class switching shapes selection dynamics
JF Science Immunology
JO Sci. Immunol.
FD American Association for the Advancement of Science
SP eabe6291
DO 10.1126/sciimmunol.abe6291
VO 6
IS 56
A1 King, Hamish W.
A1 Orban, Nara
A1 Riches, John C.
A1 Clear, Andrew J.
A1 Warnes, Gary
A1 Teichmann, Sarah A.
A1 James, Louisa K.
YR 2021
UL http://immunology.sciencemag.org/content/6/56/eabe6291.abstract
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.