Dysregulation of memory B cells and circulating T follicular helper cells is a predictor of poor immune recovery in HIV‐infected patients on antiretroviral therapy

Abstract

T follicular helper (Tfh) cells and their interactions with B cells within the germinal center play extensive roles in human immunodeficiency virus (HIV) pathology. However, their association with immune reconstitution during antiretroviral therapy (ART) is still unclear. The aim of this study was to determine the impact of Tfh and memory B cell function on T helper cell recovery in patients with acute or chronic HIV infection. A total of 100 HIV-infected individuals were enrolled in our study, classified into acute and chronic HIV infection groups (60 and 40, respectively), and subsequently classified into immunological responder (IR) and immunological nonresponder (INR) subgroups according to immune recovery outcomes after 96 weeks of ART. Liquid chromatography-mass spectrometry was used to quantify the temporal regulation patterns of B and CD4 + T-cell profiles among patients, and flow cytometry was used to investigate certain subsets of B and T cells. Here we showed that the prevalence of Tfh cells in the T helper cell population correlated negatively with CD4 + T-cell recovery. The proportion of CXCR3 − Tfh cells in patients with acute or chronic infection was associated with CD4 + T-cell count recovery, and the proportion of CD21 + memory B cells at baseline was significantly higher in those with improved immune recovery outcomes. Universal proteomic dysregulation of B and CD4 + T cells at baseline was detected in patients with acute infected and poor CD4 + T-cell recovery. Proteomics analysis revealed distinct temporal regulation profiles of both T helper cells and B cells between IRs and INRs among patients with

Cellular and molecular insights into incomplete immune recovery in HIV/AIDS patients

“…In HIV infection, B cell-mediated immune response is sustained by HIV-specific memory B cells and plasma cells ( 148 ). A recent study found that the proportions of naïve B, memory B, and plasma cells are not associated with immune recovery, while the low frequency of CD21 + memory B cells is a risk factor for incomplete immune reconstitution ( 149 ). This may be related to the dysregulation of memory B cells and circulating T follicular helper cells ( 149 , 150 ).…”

“…A recent study found that the proportions of naïve B, memory B, and plasma cells are not associated with immune recovery, while the low frequency of CD21 + memory B cells is a risk factor for incomplete immune reconstitution ( 149 ). This may be related to the dysregulation of memory B cells and circulating T follicular helper cells ( 149 , 150 ). In addition, another study found that the diversity of the B-cell receptor repertoire in HIV-INRs was decreased, and naïve B cells with low differentiation improve the immune reconstitution ( 151 ).…”

Multi-omics in HIV: searching insights to understand immunological non-response in PLHIV

“…Moreover, a recent study analyzing the baseline proteome of B cells from patients with acute HIV infection showed approximately 2500 significant proteins differentiated among groups. Specifically, the TGF-β, NF-κB and CD35 proteins were highly altered in INR compared to IR and healthy controls ( Table 1 ) ( 44 ). The enormous number of altered proteins found in this study suggests that dysregulation of B cells in HIV patients may serve as a predictor of poor CD4 + T-cell recovery.…”

“…Accordingly, it has been shown that IL-2, IL-4, IL-10, IL-17, and IFN-γ levels are significantly lower in INR than in IR ( 15 , 85 ). These cytokines are strongly involved in T-cell activation and proliferation, and their decrease might lead to their depletion ( 43 , 44 , 83 ). Interestingly, Meyer et al.…”

“…Accordingly, it has been shown that IL-2, IL-4, IL-10, IL-17, and IFN-g levels are significantly lower in INR than in IR (15, 85). These cytokines are strongly involved in T-cell activation and proliferation, and their decrease might lead to their depletion (43,44,83). Interestingly, Meyer et al showed that IL-17 levels and CD4 + T-cell counts were negatively correlated with high levels of I-FABP and REG3a in INR individuals compared with IR.…”