AUTHOR=Noto Alessandra , Suffiotti Madeleine , Joo Victor , Mancarella Antonio , Procopio Francesco A. , Cavet Guy , Leung Yvonne , Corpataux Jean-Marc , Cavassini Matthias , Riva Agostino , Stamatatos Leonidas , Gottardo Raphael , McDermott Adrian B. , Koup Richard A. , Fenwick Craig , Perreau Matthieu , Pantaleo Giuseppe TITLE=The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.960120 DOI=10.3389/fimmu.2022.960120 ISSN=1664-3224 ABSTRACT=

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-γ and dual IL-21/IFN-γ 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-γ 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.