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Suan, Dan; Nguyen, Akira; Moran, Imogen; Bourne, Katherine; Hermes, Jana R.; Arshi, Mehreen; Hampton, Henry R.; Tomura, Michio; Miwa, Yoshihiro; Kelleher, Anthony D.; Kaplan, Warren; Deenick, Elissa K.; Tangye, Stuart G.; Brink, Robert; Chtanova, Tatyana; Phan, Tri Giang
Immunity (Cambridge, Mass.), 04/2015, Letnik: 42, Številka: 4Journal Article
B helper follicular T (Tfh) cells are critical for long-term humoral immunity. However, it remains unclear how these cells are recruited and contribute to secondary immune responses. Here we show that primary Tfh cells segregate into follicular mantle (FM) and germinal center (GC) subpopulations that display distinct gene expression signatures. Restriction of the primary Tfh cell subpopulation in the GC was mediated by downregulation of chemotactic receptor EBI2. Following collapse of the GC, memory T cells persisted in the outer follicle where they scanned CD169+ subcapsular sinus macrophages. Reactivation and intrafollicular expansion of these follicular memory T cells in the subcapsular region was followed by their extrafollicular dissemination via the lymphatic flow. These data suggest that Tfh cells integrate their antigen-experience history to focus T cell help within the GC during primary responses but act rapidly to provide systemic T cell help after re-exposure to the antigen. Display omitted •Primary Tfh cells are confined to the germinal center•Follicular memory T cells scan subcapsular sinus macrophages for antigen•Secondary Tfh cells are reactivated and proliferate in the subcapsular region•Secondary Tfh cells egress from the follicle via the subcapsular sinus This study shows that Tfh cells are confined to the germinal center (GC) in the primary response and that follicular memory T cells are reactivated and proliferate in the subcapsular region. It also shows that Tfh cells are able to egress from the follicle in the secondary response.
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