| First Author | Ding Q | Year | 2017 |
| Journal | J Immunol | Volume | 199 |
| Issue | 7 | Pages | 2585-2595 |
| PubMed ID | 28848066 | Mgi Jnum | J:250713 |
| Mgi Id | MGI:6103655 | Doi | 10.4049/jimmunol.1602107 |
| Citation | Ding Q, et al. (2017) TIM-4 Identifies IFN-gamma-Expressing Proinflammatory B Effector 1 Cells That Promote Tumor and Allograft Rejection. J Immunol 199(7):2585-2595 |
| abstractText | B cells give rise to polarized subsets, including B effector 1 (Be1) cells and regulatory B cells, which can promote or inhibit immune responses through expression of IFN-gamma and IL-10, respectively. Such subsets likely explain why B cell depletion can either ameliorate or exacerbate inflammatory diseases; however, these cells remain poorly understood because of the absence of specific markers. Although T cell Ig and mucin domain-containing molecule (TIM)-1 broadly identifies IL-10(+) regulatory B cells, no similar markers for Be1 cells have been described. We now show that TIM-4 is expressed by a subset of B cells distinct from those expressing TIM-1. Although TIM-1(+) B cells are enriched for IL-10, TIM-4(+) B cells are enriched for IFN-gamma. TIM-1(+) B cells enhanced the growth of B16-F10 melanoma. In contrast, TIM-4(+) B cells decreased B16-F10 metastasis and s.c. tumor growth, and this was IFN-gamma dependent. TIM-1(+) B cells prolonged islet allograft survival in B-deficient mice, whereas TIM-4(+) B cells accelerated rejection in an IFN-gamma-dependent manner. Moreover, TIM-4(+) B cells promoted proinflammatory Th differentiation in vivo, increasing IFN-gamma while decreasing IL-4, IL-10, and Foxp3 expression by CD4(+) T cells-effects that are opposite from those of TIM-1(+) B cells. Importantly, a monoclonal anti-TIM-4 Ab promoted allograft tolerance, and this was dependent on B cell expression of TIM-4. Anti-TIM-4 downregulated T-bet and IFN-gamma expression by TIM-4(+) B cells and indirectly increased IL-10 expression by TIM-1(+) B cells. Thus, TIM-4(+) B cells are enriched for IFN-gamma-producing proinflammatory Be1 cells that enhance immune responsiveness and can be specifically targeted with anti-TIM-4. |
