title: MicroRNAs miR-155 and miR-16 Decrease AID and E47 in B Cells from Elderly Individuals.
abstract: Our research in the past few years has identified B cell-specific biomarkers able to predict optimal Ab responses in both young and elderly individuals. These biomarkers are activation-induced cytidine deaminase (AID), the enzyme of class switch recombination and somatic hypermutation; the transcription factor E47, crucial for AID expression; and the ability to generate optimal memory B cells. Moreover, we have found that the increased proinflammatory status of the elderly, both in sera and intrinsic to B cells, negatively impacts B cell function. We have now investigated whether particular inflammatory microRNAs (miRs) contribute to decreased E47 and AID in aged B cells. Our data indicate that E47 and AID mRNA stability is lower in stimulated B cells from elderly individuals. We measured the expression of two miRs crucial for class switch recombination, miR-155 and miR-16, in human unstimulated B cells from young and elderly individuals with the rationale that increases in these before stimulation would decrease E47/AID upon cell activation. We found these miRs and B cell-intrinsic inflammation upregulated in aged unstimulated B cells and negatively associated with AID in the same B cells after stimulation with CpG. We propose that the downregulation of AID in aged human B cells may occur through binding of miR-155 to the 3'-untranslated regions of AID mRNA and/or binding of miR-16 to the 3'-untranslated regions of E47 mRNA, as well as at the transcriptional level of less E47 for AID. Our results indicate novel molecular pathways leading to reduced B cell function with aging.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101 dfrasca@med.miami.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Frasca
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101.
authors.forename: Alain
authors.initials: A
authors.lastname: Diaz
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101.
authors.forename: Maria
authors.initials: M
authors.lastname: Romero
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101.
authors.forename: Franco
authors.initials: F
authors.lastname: Ferracci
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101.
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Blomberg
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D001402:B-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058127:Transcription Factor 3 / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D020413:3' Untranslated Regions; C524942:MIRN155 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D058127:Transcription Factor 3; D014409:Tumor Necrosis Factor-alpha; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase