期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 128, 期 9, 页码 4163-4178出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI99597
关键词
-
资金
- NIH [DK093695]
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 alpha(v) integrins and noncanonical autophagy. Using B cell-specific alpha(v)-KO mice, we show that loss of alpha(v)-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 alpha(v)-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.
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