WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins
B cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/23/2704 |
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| author | Abhishek Bedi Kate Choi Connor Keane Madison Bolger-Munro Ashley R. Ambrose Michael R. Gold |
| author_facet | Abhishek Bedi Kate Choi Connor Keane Madison Bolger-Munro Ashley R. Ambrose Michael R. Gold |
| author_sort | Abhishek Bedi |
| collection | DOAJ |
| description | B cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters and to form an immune synapse (IS) when interacting with antigen-presenting cells (APCs). Although the WASp, N-WASp, and WAVE nucleation-promoting factors activate the Arp2/3 complex, the role of WAVE2 in B cells has not been directly assessed. We now show that both WAVE2 and the Arp2/3 complex localize to the peripheral ring of branched F-actin when B cells spread on immobilized anti-Ig antibodies. The siRNA-mediated depletion of WAVE2 reduced and delayed B cell spreading on immobilized anti-Ig, and this was associated with a thinner peripheral F-actin ring and reduced actin retrograde flow compared to control cells. Depleting WAVE2 also impaired integrin-mediated B cell spreading on fibronectin and the LFA-1-induced formation of actomyosin arcs. Actin retrograde flow amplifies BCR signaling at the IS, and we found that depleting WAVE2 reduced microcluster-based BCR signaling and signal amplification at the IS, as well as B cell activation in response to antigen-bearing cells. Hence, WAVE2 contributes to multiple actin-dependent processes in B lymphocytes. |
| first_indexed | 2024-03-09T01:53:42Z |
| format | Article |
| id | doaj.art-44948d1e7c1244329765c77597acb64d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T01:53:42Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-44948d1e7c1244329765c77597acb64d2023-12-08T15:13:06ZengMDPI AGCells2073-44092023-11-011223270410.3390/cells12232704WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and IntegrinsAbhishek Bedi0Kate Choi1Connor Keane2Madison Bolger-Munro3Ashley R. Ambrose4Michael R. Gold5Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, CanadaDepartment of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, CanadaDepartment of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, CanadaDepartment of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, CanadaDepartment of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, CanadaDepartment of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver, BC V6T1Z3, CanadaB cell antigen receptor (BCR) signaling induces actin cytoskeleton remodeling by stimulating actin severing, actin polymerization, and the nucleation of branched actin networks via the Arp2/3 complex. This enables B cells to spread on antigen-bearing surfaces in order to increase antigen encounters and to form an immune synapse (IS) when interacting with antigen-presenting cells (APCs). Although the WASp, N-WASp, and WAVE nucleation-promoting factors activate the Arp2/3 complex, the role of WAVE2 in B cells has not been directly assessed. We now show that both WAVE2 and the Arp2/3 complex localize to the peripheral ring of branched F-actin when B cells spread on immobilized anti-Ig antibodies. The siRNA-mediated depletion of WAVE2 reduced and delayed B cell spreading on immobilized anti-Ig, and this was associated with a thinner peripheral F-actin ring and reduced actin retrograde flow compared to control cells. Depleting WAVE2 also impaired integrin-mediated B cell spreading on fibronectin and the LFA-1-induced formation of actomyosin arcs. Actin retrograde flow amplifies BCR signaling at the IS, and we found that depleting WAVE2 reduced microcluster-based BCR signaling and signal amplification at the IS, as well as B cell activation in response to antigen-bearing cells. Hence, WAVE2 contributes to multiple actin-dependent processes in B lymphocytes.https://www.mdpi.com/2073-4409/12/23/2704B cellB cell antigen receptor (BCR)antigen presenting cell (APC)F-actinWAVE2Arp2/3 complex |
| spellingShingle | Abhishek Bedi Kate Choi Connor Keane Madison Bolger-Munro Ashley R. Ambrose Michael R. Gold WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins Cells B cell B cell antigen receptor (BCR) antigen presenting cell (APC) F-actin WAVE2 Arp2/3 complex |
| title | WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins |
| title_full | WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins |
| title_fullStr | WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins |
| title_full_unstemmed | WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins |
| title_short | WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins |
| title_sort | wave2 regulates actin dependent processes induced by the b cell antigen receptor and integrins |
| topic | B cell B cell antigen receptor (BCR) antigen presenting cell (APC) F-actin WAVE2 Arp2/3 complex |
| url | https://www.mdpi.com/2073-4409/12/23/2704 |
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