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

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.