HIV remodels germinal centers through T follicular helper cell loss
- 1University of South Florida Morsani College of Medicine
Abstract
T follicular helper cells (Tfh) within germinal centers are among the most permissive cells for HIV infection and serve as a critical part of the viral reservoir. Given the key role of Tfh in affinity maturation and the production of plasma cells and memory B cells, an understanding of this critical viral reservoir is fundamental not only for cure strategies but also for understanding immunodeficiency in people living with HIV (PLWH). Using rare clinical specimens from PLWH, we demonstrate that HIV causes both a change in the cellular composition of germinal centers and changes in their overall architecture in ways that are consistent with the immunodeficiency seen in PLWH, independent of their CD4 count. We note a significant decrease in the number of GC Tfh cells and an increase in the number of follicular CD8 T cells in lymphoid tissues obtained from PLWH. Our data further show that GC size is decreased both by HIV and with increased age. Single-cell RNA sequencing data demonstrate that HIV acutely decreases the expression of Tfh B-cell support pathways and disrupts Tfh expression of cell trafficking receptors. Additionally, in a lymphoid organoid model of acute infection that forms GC-like structures, these findings are recapitulated, suggesting that New Approach Methodologies could be germane to understanding the impact of HIV on the reservoir and immunodeficiency. This study describes previously undocumented remodeling of the germinal center niche in PLWH, providing insight into the immune microenvironment of a key HIV reservoir that may help inform future cure strategies.
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BibTeX
@misc{jacobs2026remodels,
title = {{HIV remodels germinal centers through T follicular helper cell loss}},
author = {D. Jacobs and F. Abdool and L. Pohlenz and D. Curtis and R. Gill and J. P. Bush and M. Martin and J. Toman and W. Kuhn and S. Maistry and A. Levy and R. S. Veazey and M. Watkins and J. Rappaport and J. Porterfield},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.08.757815},
url = {https://www.biorxiv.org/content/10.64898/2026.10.08.757815v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - HIV remodels germinal centers through T follicular helper cell loss
AU - D. Jacobs
AU - F. Abdool
AU - L. Pohlenz
AU - D. Curtis
AU - R. Gill
AU - J. P. Bush
AU - M. Martin
AU - J. Toman
AU - W. Kuhn
AU - S. Maistry
AU - A. Levy
AU - R. S. Veazey
AU - M. Watkins
AU - J. Rappaport
AU - J. Porterfield
PY - 2026
DA - 2026/10/08
PB - bioRxiv
DO - 10.64898/2026.10.08.757815
UR - https://www.biorxiv.org/content/10.64898/2026.10.08.757815v1
AB - T follicular helper cells (Tfh) within germinal centers are among the most permissive cells for HIV infection and serve as a critical part of the viral reservoir. Given the key role of Tfh in affinity maturation and the production of plasma cells and memory B cells, an understanding of this critical viral reservoir is fundamental not only for cure strategies but also for understanding immunodeficiency in people living with HIV (PLWH). Using rare clinical specimens from PLWH, we demonstrate that HIV causes both a change in the cellular composition of germinal centers and changes in their overall architecture in ways that are consistent with the immunodeficiency seen in PLWH, independent of their CD4 count. We note a significant decrease in the number of GC Tfh cells and an increase in the number of follicular CD8 T cells in lymphoid tissues obtained from PLWH. Our data further show that GC size is decreased both by HIV and with increased age. Single-cell RNA sequencing data demonstrate that HIV acutely decreases the expression of Tfh B-cell support pathways and disrupts Tfh expression of cell trafficking receptors. Additionally, in a lymphoid organoid model of acute infection that forms GC-like structures, these findings are recapitulated, suggesting that New Approach Methodologies could be germane to understanding the impact of HIV on the reservoir and immunodeficiency. This study describes previously undocumented remodeling of the germinal center niche in PLWH, providing insight into the immune microenvironment of a key HIV reservoir that may help inform future cure strategies.
ER -