Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Dougan, Stephanie K.; Ashour, Joseph; Karssemeijer, Roos A.; Popp, Maximilian W.; Avalos, Ana M.; Barisa, Marta; Altenburg, Arwen F.; Ingram, Jessica R.; Cragnolini, Juan J.; Guo, Chunguang; Alt, Frederick W.; Jaenisch, Rudolf; Ploegh, Hidde L.

doi:10.1038/nature12637

Cited by 57 publications

(58 citation statements)

References 30 publications

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“…HA was detected by immunoblot only when expressed from the VEEV replicon. Correct processing and shuttling of the VEEV RNA-expressed HA protein to the cell surface were confirmed by surface immunostaining with an HA-specific single-chain antibody (70) (Fig. S7B).…”

Section: Resultsmentioning

confidence: 94%

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Chahal

Khan

Cooper

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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349

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Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.

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Section: Resultsmentioning

confidence: 94%

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Chahal

Khan

Cooper

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

349

260

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“…Tg(TcraTcrb)425Cbn (OT-II) mice on a Rag2 −/− background were a kind gift from Ed Palmer, University of Basel, Basel, Switzerland. FluBI mice (23) were bred from founder members provided by Stephanie Dougan and Hidde Ploegh, Whitehead Institute, Cambridge, MA. IgH MOG (ref.…”

Section: Methodsmentioning

confidence: 99%

Cocapture of cognate and bystander antigens can activate autoreactive B cells

Sanderson

Zimmermann

Eilinger

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed "bystander" antigens, might enable B-cell escape from tolerance. We tested this hypothesis using influenza hemagglutinin as a model viral antigen and transgenic, MOG-specific B cells. Using flow cytometry and live and fixed cell microscopy, we show that MOG-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. When influenza hemagglutinin is also present in the membrane of the target cell, it can be cocaptured with MOG by MOG-specific B cells via the B-cell receptor. Hemagglutinin and MOG are both presented to T cells, which in turn are activated and proliferate. As a consequence, MOG-specific B cells get help from hemagglutinin-specific T cells to produce anti-MOG antibodies. In vivo, the transfer of MOG-specific B cells into recipient mice after the cocapture of MOG and hemagglutinin leads to the production of class-switched anti-MOG antibodies, dependent on the presence of hemagglutinin-specific T cells. This mechanism offers a link between infection and autoimmunity.tolerance | autoantibodies | antigen capture | antigen presentation | influenza

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“…Camelid V H Hs, derived from the variable domain of heavy chain-only antibodies, present a unique tool (23,24). V H Hs, also referred to as nanobodies, are smaller and more stable than their traditional antibody counterparts and are less dependent on disulfide bond formation for proper folding.…”

Section: All Heavy Chain-only Antibody Variable Domains Bind Hype Whementioning

confidence: 99%

HypE-specific Nanobodies as Tools to Modulate HypE-mediated Target AMPylation

Truttmann

Qin

Stiegeler

et al. 2015

Journal of Biological Chemistry

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Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus

Cited by 57 publications

References 30 publications

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

Cocapture of cognate and bystander antigens can activate autoreactive B cells

HypE-specific Nanobodies as Tools to Modulate HypE-mediated Target AMPylation

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