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Highly functional prolonged GC-TFH responses are associated with enhanced neutralizing antibody development

ABSTRACT: T follicular helper (TFH) cells are pivotal in generating high-affinity antibodies by supporting B cell survival, proliferation, affinity maturation, and differentiation into memory B cells and plasma cells. Here, we characterized TFH cell responses to HIV Env immunization longitudinally in non-human primates, analyzing > 500,000 CD4 T cells from 192 lymph node (LN) samples collected over 60 weeks, including > 36,000 vaccine-specific TFH cells. An escalating-dose priming regimen elicited significantly higher and more sustained TFH cell responses in LNs compared to conventional bolus immunization. We observed multiple GC-TFH subpopulations, including IL4hi and IL21hi GC-TFH, which were continually present in vaccine-specific GC responses over the course of a year. Clonal tracking showed the persistence of antigen-specific TFH clones within GCs for over six months, maintaining stable gene expression profiles and showing no signs of exhaustion. TFH proliferation was observed at all timepoints, with vaccine-specific TFH proliferation detectable for 27+ weeks after priming. LN TFH subpopulations correlated strongly with HIV Env-specific antibody and neutralization titers. Additionally, we provide evidence of substantial TFH clonal migration between proximal and distal LNs. Our study underscores the importance of TFH for improving antibody responses against complex pathogens like HIV, and demonstrates GC-TFH have the capacity to survive for 48 weeks in active GC responses in the absence of any new antigen delivery.

ORGANISM(S): Macaca mulatta

PROVIDER: GSE302718 | GEO | 2025/11/07

REPOSITORIES: GEO

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