B cell–intrinsic CXCR3 drives efficient generation of ectopic pulmonary germinal center responses to influenza A virus infection

Le résumé fourni par la source

Chemotactic receptors involved in generation of ectopic pulmonary germinal centers (GCs) within inducible bronchus-associated lymphoid tissue (iBALT) are poorly defined. Here, using CIBER Cxcr3 -reporter mice, we demonstrate that the prototypical type 1 inflammatory chemokine receptor CXCR3 is highly induced in influenza A virus (IAV)-reactive B cells in the mediastinal lymph node, spleen, lung, peripheral blood, and airways following intranasal infection. Notably, elevated Cxcr3 was observed in ectopic pulmonary germinal center B (GCB) cells in iBALT relative to their contemporaneous counterparts in secondary lymphoid organs across the timecourse of the response to IAV infection. Mice with a B cell–specific deletion of Cxcr3 displayed a 50 to 60% reduction in the frequency and number of ectopic GCB cells in the lungs at the peak of the response following IAV infection, relative to controls. Furthermore, in cotransfers, Cxcr3 -deficient B cells were substantially outcompeted by their Cxcr3 -sufficient counterparts for ectopic pulmonary GC participation, but were not impacted with respect to GCB cell frequencies in other compartments. Thus, the data elucidate the requirement of B cell–intrinsic CXCR3 expression for efficient generation of ectopic pulmonary GCB cell responses in iBALT following respiratory viral infection with IAV, a finding that broadens understanding of the molecular cues underpinning this key component of local protective humoral immunity to IAV.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.