핵심기술
특허 / 논문
| Exposure of a distinct PDCA-1+ (CD317) B cell population to agonistic anti-4-1BB (CD137) inhibits T and B cell responses both in vitro and in vivo. |
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| 등록일 :2022-11-03 14:46 조회수 :2,455 |
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Exposure of a distinct PDCA-1+ (CD317) B cell population to agonistic anti-4-1BB (CD137) inhibits T and B cell responses both in vitro and in vivo. Vinay DS, Lee SJ, Kim CH, Oh HS, Kwon BS
Abstract 4-1BB (CD137) is an important T cell activating molecule. Here we report that it also promotes development of a distinct B cell subpopulation co-expressing PDCA-1. 4-1BB is expressed constitutively, and its expression is increased when PDCA-1(+) B cells are activated. We found that despite a high level of surface expression of 4-1BB on PDCA-1(+) B cells, treatment of these cells with agonistic anti-4-1BB mAb stimulated the expression of only a few activation markers (B7-2, MHC II, PD-L2), cytokines (IL-12p40/p70), and chemokines (MCP-1, RANTES), as well as sTNFR1, and the immunosuppressive enzyme, IDO. Although the PDCA-1(+) B cells stimulated by anti-4-1BB expressed MHC II at high levels and took up antigens efficiently, Ig class switching was inhibited when they were pulsed with T-independent (TI) or T-dependent (TD) Ags and adoptively transferred into syngeneic recipients. Furthermore, when anti-4-1BB-treated PDCA-1(+) B cells were pulsed with OVA peptide and combined with Vα2(+)CD4(+) T cells, Ag-specific cell division was inhibited both in vitro and in vivo. Our findings suggest that the 4-1BB signal transforms PDCA-1(+) B cells into propagators of negative immune regulation, and establish an important role for 4-1BB in PDCA-1(+) B cell development and function. |