Summary We identify the interfollicular (IF) zone as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first two days post-immunization, antigen-specific T and B cells remained confined within the IF zone, formed long-lived interactions, and upregulated the transcriptional repressor Bcl6. T cells also acquired the Tfh cell markers CXCR5, PD-1 and GL7. Responding B and T cells migrated to the follicle interior directly from the IF zone, T cell immigration preceding B cells by one day. Notably, in the absence of cognate B cells, Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS and GL7 were no longer expressed on follicular Bcl6hi T cells that nevertheless persisted in the follicle. Thus, Ag-specific B cells are required for the maintenance of the PD-1hi ICOShi GL7hi Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.

Graft-versus-host disease (GVHD) is initiated and maintained by antigenpresenting cells (APCs

Fleas are vectors for a number of pathogens including Yersinia pestis, yet factors that govern interactions between fleas and Y. pestis are not well understood. Examining gene expression changes in infected fleas could reveal pathways that affect Y. pestis survival in fleas and subsequent transmission. We used suppression subtractive hybridization to identify genes that are induced in Xenopsylla cheopis (Rothschild) (Siphonaptera: Pulicidae) in response to oral or hemocoel infection with Y. pestis. Overall, the transcriptional changes we detected were very limited. We identified several genes that are likely involved in the production or removal of reactive oxygen species (ROS). Midgut ROS levels were higher in infected fleas and antioxidant treatment before infection reduced ROS levels and resulted in higher bacterial loads. An ROS-sensitive mutant strain of Y. pestis lacking the OxyR transcriptional regulator showed reduced growth early after infection. Our results indicate that ROS may limit Y. pestis early colonization of fleas and that bacterial strategies to overcome ROS may enhance transmission.

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We identify the interfollicular (IF) zone of the lymph node as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first two days post-immunization, antigen-specific T and B cells remained confined within the IF zone, where they participated in long-lived interactions and upregulated Bcl-6, which controls the differentiation of both cell types. During this time, T cells also acquired the Tfh markers CXCR5, PD-1 and GL7. While T cell immigration into the follicle interior occurred three days post immunization, responding B cells remained largely restricted to the IF zone and the area adjacent to the sub capsular sinus at this timepoint. B cell entry into the follicle interior, and formation of nascent germinal centers, did not occur until a day later. Notably, in the absence of cognate B cells, PD-1hi Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS and GL7 expression was not maintained on T cells that nevertheless persisted within the follicle. Thus, cognate B cells are not required for Tfh cell differentiation in the IF zone, but are instead required for the long-term maintenance of the activated Tfh phenotype.