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Lino, A.C.* ; Dang, V.D.* ; Lampropoulou, V.* ; Welle, A.* ; Joedicke, J.* ; Pohar, J.* ; Simon, Q.* ; Thalmensi, J.* ; Baures, A.* ; Flühler, V.* ; Sakwa, I.* ; Stervbo, U.* ; Ries, S.* ; Jouneau, L.* ; Boudinot, P.* ; Tsubata, T.* ; Adachi, T.* ; Hutloff, A.* ; Dörner, T.* ; Zimber-Strobl, U. ; de Vos, A.F.* ; Dahlke, K.* ; Loh, G.* ; Korniotis, S.* ; Goosmann, C.* ; Weill, J.C.* ; Reynaud, C.A.* ; Kaufmann, S.H.E.* ; Walter, J.* ; Fillatreau, S.*

LAG-3 inhibitory receptor expression identifies immunosuppressive natural regulatory plasma cells.

Immunity 49, 120-133.e9 (2018)

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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.

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