The deficiency in Th2-like Tfh cells affects the maturation and quality of HIV-specific B cell response in viremic infection

• Published in: Frontiers in Immunology Vol. 13; p. 960120
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Frontiers Media SA 24.08.2022; Frontiers Media S.A
• Subjects: Cytokines; Cytokines/metabolism; Germinal Center/metabolism; HIV Infections/metabolism; Humans; Interleukin-4/metabolism; T Follicular Helper Cells; Viremia; HIV-1 infection; T helper cell; follicular T helper cells; germinal center B cells (GC B cells); lymph nodes; follicular T helper cells; Germinal Center; germinal center B cells (GC B cells); HIV Infections; HIV-1 infection; Humans; Immunologic diseases. Allergy; Immunology; Interleukin-4; lymph nodes; RC581-607; T Follicular Helper Cells; T helper cell; Viremia
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2022.960120

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.