IL-4-Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation.
J Immunol
; 200(3): 1027-1038, 2018 02 01.
Article
en En
| MEDLINE
| ID: mdl-29288206
ABSTRACT
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Activación de Linfocitos
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Receptores de Antígenos de Linfocitos B
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Flavoproteínas
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Aminoácido Oxidorreductasas
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article