Abstract
SummaryCD4+ T follicular helper cells (Tfh) promote B cell maturation and antibody production in secondary lymphoid organs. By using an innovative culture system based on splenocyte stimulation, we studied the dynamics of naive and memory CD4+ T cells during the generation of a Tfh cell response. We found that both naive and memory CD4+ T cells can acquire phenotypic and functional features of Tfh cells. Moreover, we show here that the transition of memory as well as naive CD4+ T cells into the Tfh cell profile is supported by the expression of pro-Tfh genes, including transcription factors known to orchestrate Tfh cell development. Using this culture system, we provide pieces of evidence that HIV infection differentially alters these newly identified pathways of Tfh cell generation. Such diversity in pathways of Tfh cell generation offers a new framework for the understanding of Tfh cell responses in physiological and pathological contexts.
Highlights
Within germinal centers (GCs), T follicular helper cells (Tfh) shape B cell responses by promoting the development of high-affinity antibodies, isotypic switch, and B cell maturation (Crotty, 2019; Song and Craft, 2019)
By using an innovative culture system based on splenocyte stimulation, we studied the dynamics of naive and memory CD4+ T cells during the generation of a Tfh cell response
We show here that the transition of memory as well as naive CD4+ T cells into the Tfh cell profile is supported by the expression of pro-Tfh genes, including transcription factors known to orchestrate Tfh cell development
Summary
Within germinal centers (GCs), T follicular helper cells (Tfh) shape B cell responses by promoting the development of high-affinity antibodies, isotypic switch, and B cell maturation (Crotty, 2019; Song and Craft, 2019). Tfh cells are classically identified in secondary lymphoid organs by the expression of CXCR5 and PD-1, which drive their positioning in these lymphoid organs (Sayin et al, 2018). To control B cell maturation and GC maintenance, Tfh cells express costimulatory molecules including CD40L and ICOS and secrete cytokines such as IL-21 and IL-4 (Crotty, 2019). Several in vitro experiments have shown that memory CD4+ T cells can acquire Tfh cell features upon stimulation (Jacquemin et al, 2015; Lu et al, 2011; Pattarini et al, 2017). Heterogeneous Tfh cell profiles might result from cellular plasticity in CD4+ T cell populations in lymphoid tissues
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