Transcriptomics

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Assembly of a spatial circuit of T-bet-expressing lymphocytes is required for antiviral humoral immunity


ABSTRACT: Effective antiviral immunity requires generation of T and B lymphocytes expressing transcription factor T-bet, a regulator of type 1 inflammatory responses. Using T-bet expression as an endogenous marker for cells participating in a type 1 response, we report coordinated interactions of T-bet-expressing T and B lymphocytes based on their dynamic co-localization at T cell zone and B follicle boundary (T-B boundary) and germinal centers (GC) within the draining lymph node during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches, guided by CXCR3, which enables positioning of TH1 cells at the T-B boundary. The encounter of B and TH1 cells at T-B boundary enables IFN produced by the latter to induce IgG2c class switching. Within GCs, T-bet+ TFH cells represent a specialized stable sub-lineage required for GC growth, but dispensable for IgG2c class switching. Our studies show that during respiratory viral infection, T-bet-expressing T and B lymphocytes form a circuit assembled in a spatio-temporally controlled manner that acts as a functional unit enabling a robust and coherent humoral response tailored for optimal antiviral immunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE173605 | GEO | 2021/04/30

REPOSITORIES: GEO

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