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- Title
Evolution of antigen-specific follicular helper T cell transcription from effector function to memory.
- Authors
Robinson, Amanda M.; Higgins, Brett W.; Shuparski, Andrew G.; Miller, Karen B.; McHeyzer-Williams, Louise J.; McHeyzer-Williams, Michael G.
- Abstract
Understanding how follicular helper T cells (TFH) regulate the specialization, maturation, and differentiation of adaptive B cell immunity is crucial for developing durable high-affinity immune protection. Using indexed single-cell molecular strategies, we reveal a skewed intraclonal assortment of higher-affinity T cell receptors and the distinct molecular programming of the localized TFH compartment compared with emigrant conventional effector TH cells. We find a temporal shift in B cell receptor class switch, which permits identification of inflammatory and anti-inflammatory modules of transcriptional programming that subspecialize TFH function before and during the germinal center (GC) reaction. Late collapse of this local primary GC reaction reveals a persistent post-GC TFH population that discloses a putative memory TFH program. These studies define subspecialized antigen-specific TFH transcriptional programs that progressively change with antibody class-specific evolution of high-affinity B cell immunity and a memory TFH transcriptional program that emerges upon local GC resolution. Follicular helper T cell phases: Follicular helper T cells (TFH) are critical to the development robust B cell responses, but how TFH subsets evolve and contribute to different responses is not well understood. Robinson et al. used indexed single-cell molecular analyses to define stages of TFH function in a polyclonal antigen-specific model. They observed a skewed intraclonal assortment of high-affinity TCRs associated with the TFH compartment compared to conventional effector CD4 T cells. A temporal shift in BCR class switching correlated with inflammatory and anti-inflammatory transcriptional programs in antigen-specific TFH observed before and during the germinal center (GC) reaction. In addition, collapse of the primary GC B cell response was associated with a transcriptionally distinct local memory TFH subset. These findings better define stages of TFH function and how they contribute to adaptive immunity.
- Publication
Science Immunology, 2022, Vol 7, Issue 76, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.abm2084