| First Author | Arroyo-Díaz NM | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 10 | Pages | 2358-2372.e5 |
| PubMed ID | 37699392 | Mgi Jnum | J:344107 |
| Mgi Id | MGI:7540276 | Doi | 10.1016/j.immuni.2023.08.015 |
| Citation | Arroyo-Diaz NM, et al. (2023) Interferon-gamma production by Tfh cells is required for CXCR3(+) pre-memory B cell differentiation and subsequent lung-resident memory B cell responses. Immunity 56(10):2358-2372.e5 |
| abstractText | Lung-resident memory B cells (lung-BRMs) differentiate into plasma cells after reinfection, providing enhanced pulmonary protection. Here, we investigated the determinants of lung-BRM differentiation upon influenza infection. Kinetic analyses revealed that influenza nucleoprotein (NP)-specific BRMs preferentially differentiated early after infection and required T follicular helper (Tfh) cell help. BRM differentiation temporally coincided with transient interferon (IFN)-gamma production by Tfh cells. Depletion of IFN-gamma in Tfh cells prevented lung-BRM differentiation and impaired protection against heterosubtypic infection. IFN-gamma was required for expression of the transcription factor T-bet by germinal center (GC) B cells, which promoted differentiation of a CXCR3(+) GC B cell subset that were precursors of lung-BRMs and CXCR3(+) memory B cells in the mediastinal lymph node. Absence of IFN-gamma signaling or T-bet in GC B cells prevented CXCR3(+) pre-memory precursor development and hampered CXCR3(+) memory B cell differentiation and subsequent lung-BRM responses. Thus, Tfh-cell-derived IFN-gamma is critical for lung-BRM development and pulmonary immunity, with implications for vaccination strategies targeting BRMs. |
