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Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response.

ABSTRACT: Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early memory B cells (eMBCs) that retained an AP-like transcriptional profile. Rapid decline of antigen availability controlled these events; provision of excess antigen precluded cell cycle exit and induced a new wave of PBs. Fate mapping revealed a prominent contribution of eMBCs to the MBC pool. Quiescent cells with an MBC phenotype dominated the early response to immunization in primates. A reservoir of APs/eMBCs may enable rapid readjustment of the immune response when failure to contain a threat is manifested by increased antigen availability.

SUBMITTER: Glaros V

PROVIDER: S-EPMC7612941 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response.

Glaros Vassilis V Rauschmeier René R Artemov Artem V AV Reinhardt Annika A Ols Sebastian S Emmanouilidi Aikaterini A Gustafsson Charlotte C You Yuanyuan Y Mirabello Claudio C Björklund Åsa K ÅK Perez Laurent L King Neil P NP Månsson Robert R Angeletti Davide D Loré Karin K Adameyko Igor I Busslinger Meinrad M Kreslavsky Taras T

Immunity 20210901 9

Cell fate decisions during early B cell activation determine the outcome of responses to pathogens and vaccines. We examined the early B cell response to T-dependent antigen in mice by single-cell RNA sequencing. Early after immunization, a homogeneous population of activated precursors (APs) gave rise to a transient wave of plasmablasts (PBs), followed a day later by the emergence of germinal center B cells (GCBCs). Most APs rapidly exited the cell cycle, giving rise to non-GC-derived early mem ...[more]

PMID: 34525339

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Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response.

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Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response.

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