| Autor: |
Kwak, Kihyuck, Sohn, Haewon, George, Rachel, Torgbor, Charles, Manzella-Lapeira, Javier, Brzostowski, Joseph, Pierce, Susan K. |
| Předmět: |
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| Zdroj: |
Science Signaling; 9/26/2023, Vol. 16 Issue 804, p1-15, 15p |
| Abstrakt: |
The demand for a vaccine for coronavirus disease 2019 (COVID-19) highlighted gaps in our understanding of the requirements for B cell responses to antigens, particularly to membrane-presented antigens, as occurs in vivo. We found that human B cell responses to membrane-presented antigens required the function of Piezo1, a plasma membrane mechanosensitive cation channel. Simply making contact with a glass probe induced calcium (Ca2+) fluxes in B cells that were blocked by the Piezo1 inhibitor GsMTx4. When placed on glass surfaces, the plasma membrane tension of B cells increased, which stimulated Ca2+ influx and spreading of B cells over the glass surface, which was blocked by the Piezo1 inhibitor OB-1. B cell responses to membrane-presented antigens but not to soluble antigens were inhibited both by Piezo1 inhibitors and by siRNA-mediated knockdown of Piezo1. Thus, the activation of Piezo1 defines an essential event in B cell activation to membrane-presented antigens that may be exploited to improve the efficacy of vaccines. Editor's summary: The activation of B cells upon the binding of antigens to the B cell receptor (BCR) is important for vaccine-based antibody production. B cells are more strongly activated by membrane-bound than by soluble antigens. Through imaging and functional analyses, Kwak et al. showed that the mechanosensitive cation channel Piezo1 was required for B cells to respond to antigens that were membrane-presented, but not soluble ones. Piezo1-mediated changes in Ca2+ flux enabled B cells to sense contact with a solid, antigen-bearing surface, leading to BCR activation. These findings may aid in the design of vaccines that better stimulate antibody production by B cells. —John F. Foley [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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