| First Author | Raso F | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 9 | Pages | 4163-4178 |
| PubMed ID | 29999501 | Mgi Jnum | J:266335 |
| Mgi Id | MGI:6202800 | Doi | 10.1172/JCI99597 |
| Citation | Raso F, et al. (2018) alphav Integrins regulate germinal center B cell responses through noncanonical autophagy. J Clin Invest 128(9):4163-4178 |
| abstractText | Germinal centers (GCs) are major sites of clonal B cell expansion and generation of long-lived, high-affinity antibody responses to pathogens. Signaling through TLRs on B cells promotes many aspects of GC B cell responses, including affinity maturation, class switching, and differentiation into long-lived memory and plasma cells. A major challenge for effective vaccination is identifying strategies to specifically promote GC B cell responses. Here, we have identified a mechanism of regulation of GC B cell TLR signaling, mediated by alphav integrins and noncanonical autophagy. Using B cell-specific alphav-KO mice, we show that loss of alphav-mediated TLR regulation increased GC B cell expansion, somatic hypermutation, class switching, and generation of long-lived plasma cells after immunization with virus-like particles (VLPs) or antigens associated with TLR ligand adjuvants. Furthermore, targeting alphav-mediated regulation increased the magnitude and breadth of antibody responses to influenza virus vaccination. These data therefore identify a mechanism of regulation of GC B cells that can be targeted to enhance antibody responses to vaccination. |
