title: IL-7 modulates B cells survival and activation by inducing BAFF and CD70 expression in T cells.
abstract: Interleukin-7 (IL-7) promotes the maintenance and activation of peripheral T cells, whereas it does not act directly on mature B cells due to the lack of IL-7Rα expression on these. We report here that, in spite of the insensitivity of B cells to IL-7, high concentration of IL-7 can lead to increased B cell survival and antibody production in the presence of T cells, without the use of any further B cell stimulatory signal. IL-7 promoted B cell activation through inducing CD70 expression on resting T cells, particularly on CD4+ memory cells. The interaction of CD70 molecules with the B cell costimulatory receptor CD27 led to B cell proliferation, the accumulation of CD38 + CD20- plasmablasts and antibody production. In addition, IL-7 treatment induced BAFF secretion from resting peripheral T cells thereby promoting B cell survival. IL-7 levels can increase in lymphopenic conditions, in autoimmune diseases or in patients receiving T cell regenerative IL-7 therapy. Based on our findings high IL-7 levels can lead to increased B cell activation by inducing the B cell regulatory proteins CD70 and BAFF in resting T cells. Such activity might be beneficial in short term immune-stimulatory IL-7 therapies; permanently increased IL-7 levels, on the other hand, can contribute to impaired B cell tolerance.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, Stockholm 17177, Sweden.
authors.forename: Stefano
authors.initials: S
authors.lastname: Sammicheli
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ruffin
authors.forename: Rebecka
authors.initials: R
authors.lastname: Lantto
authors.forename: Nancy
authors.initials: N
authors.lastname: Vivar
authors.forename: Francesca
authors.initials: F
authors.lastname: Chiodi
authors.forename: Bence
authors.initials: B
authors.lastname: Rethi
mesh_terms: D053264:B-Cell Activating Factor / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D053282:CD27 Ligand / Q000378:metabolism*; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015851:Interleukin-7 / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
chemical_list: D053264:B-Cell Activating Factor; D053282:CD27 Ligand; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015851:Interleukin-7