Persistent B Cell–Derived MHC Class II Signaling Is Required for the Optimal Maintenance of Tissue-Resident Helper T Cells

Emerging studies have identified the critical roles of tissue-resident memory CD8⁺ T (T_RM) and B (B_RM) cells in the protection against mucosal viral infections, but the underlying mechanisms regulating robust development of T_RM and B_RM cells remain incompletely understood. We have recently shown that tissue-resident helper CD4⁺ T (T_RH) cells, developed following influenza virus infection, function to sustain the optimal maintenance of T_RM and B_RM cells at the mucosal surface. In this study, we have explored the cellular and molecular cues modulating lung T_RH persistence after influenza infection in C57BL/6 mice. We found that T_RH cells were colocalized in tertiary lymphoid structures (TLSs) with local B cells. Abolishing TLSs or the depletion of B cells impaired lung T_RH cell numbers. Of note, we found that persistent TCR signaling is needed for the maintenance of T_RH cells after the clearance of infectious influenza virus. Furthermore, selective ablation of B cell–derived MHC class II resulted in partial reduction of lung T_RH cell number after influenza infection. Our findings suggest that the interaction between lung-resident T_RH cells and B cells, along with persistent Ag stimulation, is required to maintain T_RH cells after respiratory viral infection.