2022
DOI: 10.21203/rs.3.rs-1260549/v1
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Antigen footprint governs activation of the B cell receptor

Abstract: Antigen binding by B cell receptors (BCRs) on cognate B cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution of BCRs is on the naïve B cell and how antigen binding triggers the first step in BCR signaling. Using DNA-PAINT super-resolution microscopy, we find that most BCRs are present as monomers, dimers, or lower-order oligomers on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30 nm. We leverage a Holliday junction nanosca… Show more

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Cited by 1 publication
(3 citation statements)
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References 55 publications
(59 reference statements)
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“…Our results indicate that displaying an antigen on the exosome surface dramatically increases its immunogenicity and ability to protect against viral disease. This is not surprising, as the densely clustered array of spike trimers on the surface of spike Δ -EMAD13 exosomes resembles the artifically clustered antigens shown previously to enhance B-cell signaling in response to antigen (18,19). Moreover, antigen-display exosomes represent a safe, inexpensive, and lowtechnology approach to vaccine design and manufacture, as we were able to produce spike Δ -EMAD13 exosomes at yields of 2,200 1x doses per liter of culture medium.…”
Section: Properties Of the Spike δ -Emad13 Exosome Vaccinesupporting
confidence: 73%
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“…Our results indicate that displaying an antigen on the exosome surface dramatically increases its immunogenicity and ability to protect against viral disease. This is not surprising, as the densely clustered array of spike trimers on the surface of spike Δ -EMAD13 exosomes resembles the artifically clustered antigens shown previously to enhance B-cell signaling in response to antigen (18,19). Moreover, antigen-display exosomes represent a safe, inexpensive, and lowtechnology approach to vaccine design and manufacture, as we were able to produce spike Δ -EMAD13 exosomes at yields of 2,200 1x doses per liter of culture medium.…”
Section: Properties Of the Spike δ -Emad13 Exosome Vaccinesupporting
confidence: 73%
“…Given that B-cells respond particularly well to clustered antigen arrays (18,19), we asked whether injection of spike Δ -EMAD13 exosomes would induce protective immunity to SARS-CoV-2 at low levels of antigen, and whether it could do so without adjuvant. Spike Δ -EMAD13 exosomes were produced by inoculating 1x 10^9 FtetP::Spike Δ -EMAD13 cells into 0.5L chemically defined medium supplemented with doxycycline, shaking the cells three days, then purifying spike Δ -EMAD13 exosomes by sterilizing filtration, concentrating filtration, and size exclusion chromatography.…”
Section: Spike δ -Emad13 Exosomes Induce Protective Immunity To Sars-...mentioning
confidence: 99%
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