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

First Author  Mendoza A Year  2021
Journal  Sci Immunol Volume  6
Issue  60 PubMed ID  34117110
Mgi Jnum  J:321878 Mgi Id  MGI:6871830
Doi  10.1126/sciimmunol.abi4710 Citation  Mendoza A, et al. (2021) Assembly of a spatial circuit of T-bet-expressing T and B lymphocytes is required for antiviral humoral immunity. Sci Immunol 6(60):eabi4710
abstractText  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-gamma 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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