Germinal centers B-cell reaction and T follicular helper cells in response to HIV-1 infection

Abstract

Purpose of the review: This review aims to summarize the recent findings on germinal centers (GCs) B-cell reaction and Tfh cells in HIV-1 infection, with particular emphasis on the spatial organization of the GC, follicular cell regulation, and cellular alterations resulting from HIV infection. Recent findings: HIV-specific bNAbs are generated by iterative cycles of B cell maturation supported by GC environment. Recent observations underline that GC structural alterations at the earliest stages of HIV infection could impact Tfh and GC B cell homeostasis, thus preventing the rise of efficient humoral immunity. Moreover, despite ART treatment, HIV-derived antigens persist, particularly in follicular CD4+ T cells. Antigenic persistence and variability lead to unregulated chronic stimulation. In this context, regulation of the GC appears of special interest. In addition to follicular T regulatory cells (Tfr), new potent regulators of GC reaction such as follicular CD8 T cells have been recently identified. Summary: Altogether these new data provide a better understanding on how HIV infection severely impacts GC reaction. Here we propose several therapeutic approaches to promote the bNAbs development in HIV-infected patients by improving the preservation of GC architecture and its regulation.

IgG Antibody Responses and Immune Persistence of Two Doses of BBIBP-CorV Vaccine or CoronaVac Vaccine in People Living with HIV (PLWH) in Shenzhen, China

“…Our study found that the S-RBD-IgG antibody seropositivity rates and antibody levels were lower in PLWH at 28 ± 7 days after two doses of the BBIBP-CorV vaccine or the CoronaVac vaccine than in the HCs, which was consistent with the findings of previous studies [7][8][9]. The structural alterations in the germinal center of PLWH may affect T follicular helper cell and germinal center B cell homeostasis, thereby preventing the elevation of effective humoral immunity [10]. Therefore, humoral immune responses between PLWH and healthy individuals are generally comparable.…”

COVID-19 Vaccination in People Living with HIV (PLWH) in China: A Cross Sectional Study of Vaccine Hesitancy, Safety, and Immunogenicity

“…In line with previous studies, CD4 + T cells, especially T-follicular helper (Tfh) cells, are required for the induction of high-affinity antibody responses and the formation of longlived B cell memory. The structural changes in the germinal center and functionally altered Tfh cells derived by HIV replication and the consequent impaired interaction between Tfh cells and germinal center B cells might contribute to impaired immune response [36,37]. In addition, a third booster shot of a COVID-19 vaccine was reported to potentially provide more protection in the general population [38].…”

Effective and targeted latency reversal in CD4 + T cells from individuals on long term combined antiretroviral therapy initiated during chronic HIV-1 infection

“…Immunohistochemistry-based studies helped to establish the idea that CD4 + T cell activation and exhaustion was mostly related to the ongoing infection surrounding germinal centres [ 46–48 ]. Thus, a latent HIV-1 infection during the transition of activated T cells to memory T cells could lead to establishment of latently infected CD4 + T cell populations, mostly within the T cell zones surrounding the HIV-1-specific germinal centres [ 49 ]. Density of these proliferating T cells surrounding the HIV-1-specific germinal centres may focus replication to these T cell zones and reduce HIV-1 migration/diffusion into other antigen-specific germinal centres [ 31 ].…”