Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection

Xiaofan Lu, Xin Zhang, Allen Ka Loon Cheung, Christiane Moog, Huan Xia, Zhen Li, Rui Wang, Yunxia Ji, Wei Xia, Zhiying Liu, Lin Yuan, Xiuwen Wang, Hao Wu, Tong Zhang*, Bin Su*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Interactions between T follicular helper (Tfh) cells and germinal center B cells are essential for the differentiation of B cells and specific antibody responses against HIV-1 infection. However, the extent to which HIV-1 infection affects the dynamic interplay between these two cell populations in the bloodstream remains unclear. In this study, the dynamics of circulating Tfh (cTfh) and B cells and their relationship in individuals with acute and chronic HIV-1 infection were investigated. Twenty-five study subjects were enrolled from the Beijing PRIMO clinical cohort, a prospective cohort of HIV-1-negative men who have sex with men (MSM) for the identification of cases of acute HIV-1 infection (AHI) at Beijing Youan Hospital, Capital Medical University. Individuals with AHI were selected at random. Matched samples were also collected and analyzed from the same patients with chronic HIV-1 infection. None of the study subjects received antiretroviral therapy during acute or chronic infection. Multicolor flow cytometry was used for the immunophenotypic and functional characterization of cTfh cell and B cell subsets. AHI resulted in increased proportions in bulk cTfh, ICOS+cTfh or IL-21+ICOS+cTfh cells. In both acute and chronic infections, activated memory (AM), tissue-like memory (TLM), and plasmablast (PB) B cell levels were increased whilst resting memory (RM) and naïve mature (NM) B cell levels were decreased. Classical memory (CM) B cells were unaffected during infection. Association analyses showed that the levels of ICOS+cTfh and IL-21+ICOS+cTfh cells were negatively correlated with those of AM, CM, RM cells, and positively correlated with those of NM cells in AHI but not chronic HIV-1 infection stage (CHI). Moreover, the frequency of IL-21+ICOS+cTfh cells was also positively correlated with plasma HIV-1 viral load, and had an opposite association trend with CD4+T cell count in AHI. Our data suggests that HIV-1 infection drives the expansion of cTfh cells, which in turn leads to perturbations of B cell differentiation through ICOS signaling during acute infection stage. These findings provide insight on the role of ICOS in the regulation of cTfh/B cell interaction during AHI and may potentially guide the design of effective strategies for restoring anti-HIV-1 immunity in the infected patients.

Original languageEnglish
Article number837921
Number of pages12
JournalFrontiers in Immunology
Volume13
DOIs
Publication statusPublished - 10 Feb 2022

Scopus Subject Areas

  • Immunology and Allergy
  • Immunology

User-Defined Keywords

  • acute HIV-1 infection
  • B cells
  • ICOS
  • IL-21
  • T follicular helper cells

Fingerprint

Dive into the research topics of 'Abnormal Shift in B Memory Cell Profile Is Associated With the Expansion of Circulating T Follicular Helper Cells via ICOS Signaling During Acute HIV-1 Infection'. Together they form a unique fingerprint.

Cite this