Journal
FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.960120
Keywords
lymph nodes; follicular T helper cells; germinal center B cells (GC B cells); HIV-1 infection; T helper cell
Categories
Funding
- Swiss National Science Foundation
- Freedom Forever Association
- Bill and Melinda Gates Foundation
- [320030_200912]
- [OPP_1114725]
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The imbalance between Th2 and Th1-like Tfh cells affects B cell responses in viremic HIV infection. The decrease in Th2-like Tfh cells is related to the decrease in HIV-specific B cells, while the increase in Th1-like Tfh cells is associated with the increase in T-bet and CXCR3 expressing HIV-specific B cells. IL-4 and IL-21 cytokines promote efficient maturation of HIV-specific B cells, while IFN-gamma induces the expression of T-bet and CXCR3 in B cells. CXCR3(+) B cells have a lower rate of somatic hypermutation compared to CXCR3(-) B cells.
Optimal T follicular helper (Tfh) cells function is important to promote the development of germinal centers and maturation of high affinity antigen-specific B cells. We have found that the expression of CXCR3 defines distinct Tfh subsets: CXCR3(+) Th1-like Tfh cells mainly producing single IFN-gamma and dual IL-21/IFN-gamma and CXCR3(-) Th2-like Tfh cells mainly producing single IL-4 and dual IL-21/IL-4 cytokines. CXCR3(-) Th2-like Tfhs are significantly reduced during ongoing HIV replication. While the percentage of Th2-like Tfh cells correlates with that of total and cycling HIV-specific B cells, the percentage of CXCR3(+) Th1-like Tfhs correlates with HIV-specific B cells expressing T-bet and CXCR3. Of note, only IL-4 and IL-21 cytokines boosted efficient maturation of HIV-specific B cells while IFN-gamma induced expression of T-bet and CXCR3 in B cells. Interestingly, total and HIV-specific CXCR3(+) B cells showed lower rate of somatic hypermutation, as compared to CXCR3(-) B cells. Therefore, the imbalance in Th2/Th1-like Tfhs affects B cell responses in viremic HIV infection.
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