IL-21 from IFN-g +IL-21 +hybrid T cells promotes germinal center B cell proliferation

Abstract Clearance of infection with Plasmodium spp. requires both antibody and Th1-type responses. While Th1-like cells control the peak in P. chabaudi infection, however specific IgG is delayed. Both Tfh GC-Tfh can promote antibodies long-lived plasma to fully clear infection. numbers remain stable throughout while Th1/Tfh hybrid (IFN-g +/IL-21 +CXCR5 int) expand. Testing if triple cytokine reporter mice (Il21-Kat Il4-GFP Ifng/Thy1.1 Knock-In) report functionality accurately, we confirmed that Tfh-like Il-21 +Ifng −cells were enriched for GC (CXCR5 hiPD-1 hiCXCR6 −) majority Ifng +Il21 +cells CXCR5 intCXCR6 +. appear functional sooner than +with expression CCR7 intand Il4 +as early as day 5p.i. Transfer cytokine-expressing subsets from Il21 −/−Ifng-Thy1.1 KI into T cell deficient recipients, which are then infected chabaudi, also shows −Tfh-like 8 functional. −cell recipients generated more B cells, larger GCs parasite-specific compared other groups. +hybrid promoted GCs, but +T WT or −/−mice did not. As larger, not numerous, −recipient spleens, hypothesized proliferation was increased. Indeed, there BrdU +dark zone (CXCR4 +CD86 GCB groups, particularly IL-21 KO. Combined, this data suggests promotes vivo, though less −T cells. R01AI13506101