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LAG-3 Inhibitory Receptor Expression Identifies Immunosuppressive Natural Regulatory Plasma Cells

2018; Cell Press; Volume: 49; Issue: 1 Linguagem: Inglês

10.1016/j.immuni.2018.06.007

1097-4180

Andreia C. Lino, Van Duc Dang, Vicky Lampropoulou, Anna Welle, Jara J. Joedicke, Jelka Pohar, Quentin Simon, Jessie Thalmensi, Aurelia Baures, Vinciane Flühler, Imme Sakwa, Ulrik Stervbo, Stefanie Ries, Luc Jouneau, Pierre Boudinot, Takeshi Tsubata, Takahiro Adachi, Andreas Hutloff, Thomas Dörner, Ursula Zimber‐Strobl, Alex F. de Vos, Katja Dahlke, Gunnar Loh, Sarantis Korniotis, Christian Goosmann, Jean‐Claude Weill, Claude‐Agnès Reynaud, Stefan H. E. Kaufmann, Jörn Walter, Simon Fillatreau,

Immune Cell Function and Interaction

B lymphocytes can suppress immunity through interleukin (IL)-10 production in infectious, autoimmune, and malignant diseases. Here, we have identified a natural plasma cell subset that distinctively expresses the inhibitory receptor LAG-3 and mediates this function in vivo. These plasma cells also express the inhibitory receptors CD200, PD-L1, and PD-L2. They develop from various B cell subsets in a B cell receptor (BCR)-dependent manner independently of microbiota in naive mice. After challenge they upregulate IL-10 expression via a Toll-like receptor-driven mechanism within hours and without proliferating. This function is associated with a unique transcriptome and epigenome, including the lowest amount of DNA methylation at the Il10 locus compared to other B cell subsets. Their augmented accumulation in naive mutant mice with increased BCR signaling correlates with the inhibition of memory T cell formation and vaccine efficacy after challenge. These natural regulatory plasma cells may be of broad relevance for disease intervention.