title: MicroRNAs prevent the generation of autoreactive antibodies.
abstract: MicroRNAs have been shown to be critical for a number of aspects of immune system regulation and function. Here, we have examined the role of microRNAs in terminal B cell differentiation by analyzing Cd19-Cre(ki/+) Dicer1(fl/fl) mice. We found that in the absence of Dicer, the transitional and marginal zone (MZ) B cell compartments were overrepresented and follicular (FO) B cell generation was impaired. microRNA analysis revealed that miR185, a microRNA overexpressed in FO cells, dampened B cell receptor (BCR) signaling through Bruton tyrosine kinase downregulation. Dicer-deficient B cells had a skewed BCR repertoire with hallmarks of autoreactivity, which correlated with high titers of autoreactive antibodies in serum and autoimmune features in females. Together, our results reveal a crucial role for microRNAs in late B cell differentiation and in the establishment of B cell tolerance.
authors.affiliation: DNA Hypermutation and Cancer Group, Spanish National Cancer Research Center (CNIO), Madrid 28029, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Belver
authors.forename: Virginia G
authors.initials: VG
authors.lastname: de Yébenes
authors.forename: Almudena R
authors.initials: AR
authors.lastname: Ramiro
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D053487:DEAD-box RNA Helicases / Q000235:genetics; D015536:Down-Regulation; D004722:Endoribonucleases / Q000235:genetics; D005260:Female; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D043244:Ribonuclease III
chemical_list: D018941:Antigens, CD19; D001323:Autoantibodies; D035683:MicroRNAs; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases