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HIV‐1 infection of CD4 T cells impairs antigen‐specific B cell function

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Failures to produce neutralizing antibodies upon HIV‐1 infection result in part from B‐cell dysfunction due to unspecific B‐cell activation. How HIV‐1 affects antigen‐specific B‐cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, w...

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Hauptverfasser: Kaw, Sheetal (VerfasserIn) , Ananth, Swetha (VerfasserIn) , Tsopoulidis, Nikolaos (VerfasserIn) , Morath, Katharina (VerfasserIn) , Coban, Bahar M (VerfasserIn) , Hohenberger, Ralph (VerfasserIn) , Bulut, Cem (VerfasserIn) , Klein, Florian (VerfasserIn) , Stolp-Rastätter, Bettina (VerfasserIn) , Fackler, Oliver Till (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 4 November 2020
In: The EMBO journal
Year: 2020, Jahrgang: 39, Heft: 24, Pages: 1-18
ISSN:1460-2075
DOI:10.15252/embj.2020105594
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/embj.2020105594
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/embj.2020105594
Volltext
Verfasserangaben:Sheetal Kaw, Swetha Ananth, Nikolaos Tsopoulidis, Katharina Morath, Bahar M Coban, Ralph Hohenberger, Olcay C Bulut, Florian Klein, Bettina Stolp & Oliver T Fackler
Beschreibung
Zusammenfassung:Failures to produce neutralizing antibodies upon HIV‐1 infection result in part from B‐cell dysfunction due to unspecific B‐cell activation. How HIV‐1 affects antigen‐specific B‐cell functions remains elusive. Using an adoptive transfer mouse model and ex vivo HIV infection of human tonsil tissue, we found that expression of the HIV‐1 pathogenesis factor NEF in CD4 T cells undermines their helper function and impairs cognate B‐cell functions including mounting of efficient specific IgG responses. NEF interfered with T cell help via a specific protein interaction motif that prevents polarized cytokine secretion at the T‐cell-B‐cell immune synapse. This interference reduced B‐cell activation and proliferation and thus disrupted germinal center formation and affinity maturation. These results identify NEF as a key component for HIV‐mediated dysfunction of antigen‐specific B cells. Therapeutic targeting of the identified molecular surface in NEF will facilitate host control of HIV infection.
Beschreibung:Gesehen am 18.12.2023
Beschreibung:Online Resource
ISSN:1460-2075
DOI:10.15252/embj.2020105594

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