| First Author | Bod L | Year | 2018 |
| Journal | J Immunol | Volume | 200 |
| Issue | 3 | Pages | 1027-1038 |
| PubMed ID | 29288206 | Mgi Jnum | J:258123 |
| Mgi Id | MGI:6113164 | Doi | 10.4049/jimmunol.1601609 |
| Citation | Bod L, et al. (2018) IL-4-Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation. J Immunol 200(3):1027-1038 |
| abstractText | Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4-induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells. They also present a higher serum level of natural Igs and self-reactive Abs. We also demonstrate that IL4I1 produced by B cells themselves controls the germinal center reaction, plasma cell differentiation, and specific Ab production in response to T dependent Ags, SRBC, and NP-KLH. In vitro, IL4I1-deficient B cells proliferate more efficiently than their wild-type counterparts in response to BCR cross-linking. Moreover, the absence of IL4I1 increases activation of the Syk-Akt-S6kinase signaling pathway and calcium mobilization, and inhibits SHP-1 activity upon BCR engagement, thus supporting that IL4I1 negatively controls BCR-dependent activation. Overall, our study reveals a new perspective on IL4I1 as a key regulator of B cell biology. |
