This review aims to summarize the recent findings on germinal center B-cell reaction and Tfh cells in HIV-1 infection, with particular emphasis on the spatial organization of the germinal center, follicular cell regulation, and cellular alterations resulting from HIV infection.
HIV-specific bNAbs are generated by iterative cycles of B-cell maturation supported by GC environment. Recent observations underline that germinal center structural alterations at the earliest stages of HIV infection could impact Tfh cell and germinal center 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 germinal center appears of special interest. In addition to follicular T-regulatory cells (Tfr), new potent regulators of germinal center reaction, such as follicular CD8 T and NK cells have been recently identified.
Altogether these new data provide a better understanding on how HIV infection severely impacts germinal center reaction. Here we propose several therapeutic approaches to promote the bNAb development in HIV-infected patients by improving the preservation of germinal center architecture and its regulation.
Sorbonne Université, Inserm, CNRS, Centre d’Immunologie et des Maladies Infectieuses Cimi-Paris, Paris, France
Correspondence to Stéphanie Graff-Dubois, UMRS - 959 Inserm - Sorbonne Université, GH Pitié Salpêtrière - Bat. Cervi, 83 Bd de l’Hôpital, 75651 Paris Cedex 13, France. . Tel: +33 1 42 17 74 77; e-mail: firstname.lastname@example.org