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

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Science Immunology  11 Jun 2021:
Vol. 6, Issue 60, eabi4710
DOI: 10.1126/sciimmunol.abi4710

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The right place at the right time

Protective humoral immunity against viral infections requires an effective type 1 immune response by germinal center (GC) T and B cells, a hallmark of which is expression of the transcription factor T-bet. Mendoza et al. examined the coordinated activity of distinct T-bet–expressing lymphocyte populations during influenza infection in mice, demonstrating that CXCR3-mediated localization of T-bet+ TH1 cells to the T-B boundary opposite T-bet+ B cells is required for GC B cell class switching to antiviral IgG2c. Conversely, T-bet+ T follicular helper cells controlled the magnitude of the GC B cell response but were dispensable for IgG2c class switching. These results demonstrate that the activity of T-bet+ T and B cells are spatiotemporally coordinated to control distinct features of the humoral response to viral infection.


Effective antiviral immunity requires generation of T and B lymphocytes expressing the 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 on the basis of their dynamic colocalization at the T cell zone and B follicle boundary (T-B boundary) and germinal centers (GCs) during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches within the draining lymph node, guided by CXCR3 that enables positioning of TH1 cells at the T-B boundary. The encounter of B and TH1 cells at the T-B boundary enables IFN-γ produced by the latter to induce IgG2c class switching. Within GCs, T-bet+ TFH cells represent a specialized stable sublineage 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 spatiotemporally controlled manner that acts as a functional unit enabling a robust and coherent humoral response tailored for optimal antiviral immunity.

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