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Article Dans Une Revue Journal of Immunology Année : 2018

IL-4–Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation

Lloyd Bod
  • Fonction : Auteur
Laetitia Douguet
  • Fonction : Auteur
Cédric Auffray
  • Fonction : Auteur
Renée Lengagne
  • Fonction : Auteur
Fériel Bekkat
  • Fonction : Auteur
Elena Rondeau
  • Fonction : Auteur
Valérie Molinier-Frenkel
  • Fonction : Auteur
Flavia Castellano
Yolande Richard
Armelle Prévost-Blondel

Résumé

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.

Dates et versions

hal-03993671 , version 1 (17-02-2023)

Identifiants

Citer

Lloyd Bod, Laetitia Douguet, Cédric Auffray, Renée Lengagne, Fériel Bekkat, et al.. IL-4–Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation. Journal of Immunology, 2018, 200 (3), pp.1027-1038. ⟨10.4049/jimmunol.1601609⟩. ⟨hal-03993671⟩

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