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

Jeger-Madiot, Raphaël; Heredia, Maud; Graff-Dubois, Stéphanie

Current Opinion in HIV and AIDS: July 2019 - Volume 14 - Issue 4 - p 246–252
doi: 10.1097/COH.0000000000000557
BROAD NEUTRALISING AND NON-NEUTRALISING ANTIBODIES: Edited by Hugo Mouquet and Olivier Schwartz
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Purpose of review 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.

Recent findings 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.

Summary 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: stephanie.graff-dubois@sorbonne-universite.fr

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