An Integrated Signaling Threshold Initiates IgG Response toward Virus-like Immunogens.

Autor:	Wholey WY; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI., Meyer AR; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI., Yoda ST; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI., Mueller JL; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA., Mathenge R; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA., Chackerian B; Department of Molecular Genetics and Microbiology, School of Medicine, University of New Mexico, Albuquerque, NM., Zikherman J; Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA., Cheng W; Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI.; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2024 Oct 15; Vol. 213 (8), pp. 1061-1075.
DOI:	10.4049/jimmunol.2400101
Abstrakt:	Class-switched neutralizing Ab (nAb) production is rapidly induced upon many viral infections. However, due to the presence of multiple components in virions, the precise biochemical and biophysical signals from viral infections that initiate nAb responses remain inadequately defined. Using a reductionist system of synthetic virus-like structures, in this study, we show that a foreign protein on a virion-sized liposome can serve as a stand-alone danger signal to initiate class-switched nAb responses without T cell help or TLR but requires CD19. Introduction of internal nucleic acids (iNAs) obviates the need for CD19, lowers the epitope density (ED) required to elicit the Ab response, and transforms these structures into highly potent immunogens that rival conventional virus-like particles in their ability to elicit strong Ag-specific IgG. As early as day 5 after immunization, structures harboring iNAs and decorated with just a few molecules of surface Ag at doses as low as 100 ng induced all IgG subclasses of Ab in mice and reproduced the IgG2a/2c restriction that is long observed in live viral infections. These findings reveal a shared mechanism for the nAb response in mice. High ED is capable but not necessary for driving Ab secretion. Instead, even a few molecules of surface Ag, when combined with nucleic acids within these structures, can trigger strong IgG production. As a result, the signaling threshold for induction of IgG in individual B cells is set by dual signals originating from both ED on the surface and the presence of iNAs within viral particulate immunogens. (Copyright © 2024 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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