| First Author | Melcher C | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 2 | Pages | 111051 |
| PubMed ID | 35830810 | Mgi Jnum | J:326622 |
| Mgi Id | MGI:7316243 | Doi | 10.1016/j.celrep.2022.111051 |
| Citation | Melcher C, et al. (2022) B cell-mediated regulatory mechanisms control tumor-promoting intestinal inflammation. Cell Rep 40(2):111051 |
| abstractText | Mechanisms underlying tumor-promoting inflammatory processes in colitis-associated colorectal cancer (CAC) remain largely elusive. Here, we provide genetic evidence for distinct B cell-mediated immunoregulatory mechanisms that protect from chronic colitis versus CAC. We demonstrate an inherent capacity of interleukin-10 (IL-10)-producing B cells to differentiate into immunoglobulin A (IgA) plasma cells (PCs) upon Toll-like receptor (TLR) activation. Our data show that B cell-derived IL-10 is essential to limit pathogenic T helper type 1 (Th1)/Th17 T cell responses during chronic colitis, while IgA PCs derived from IL-10(+) B cells are being implicated in restraining tumorigenesis during CAC. Formation of a tumor-protective intestinal environment was associated with clonal expansion of specific types of colonic IgA PCs and development of an altered microbiota that attenuated CAC. We thus propose that regulatory B cell-mediated immunomodulation entails temporal release of IL-10, which is superseded by the generation of specific IgA affecting the microbial community, thereby controlling chronic inflammation and tumorigenesis in a distinctive but interrelated manner. |
