title: TLR9-signaling is required for turning retinoic acid into a potent stimulator of RP105 (CD180)-mediated proliferation and IgG synthesis in human memory B cells.
abstract: The role of vitamin A in the various parts of the immune system remains elusive. Toll-like receptors (TLRs) are involved in innate polyclonal activation of B-cells, and as such they are important for maintaining long-lasting first line defense against pathogens. Here we explore the impact of all-trans retinoic acid (RA) on B cell responses mediated via the TLR homolog RP105 (CD180). We show that RA slightly reduces the proliferation and IgG production in CD27+ memory B cells stimulated by anti-RP105 alone. However, co-stimulation with the TLR9-ligand CpG results in turning RA into a potent stimulator of RP105-induced proliferation and IgG synthesis in memory B cells. The results emphasize the important role of RA in stimulating TLR-mediated polyclonal activation and differentiation of B cells, and reveal the complex interplay between various TLRs that may underlie the ability of RA to fight pathogens.
authors.affiliation: Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. a.b.eriksen@medisin.uio.no
authors.forename: Agnete Bratsberg
authors.initials: AB
authors.lastname: Eriksen
authors.forename: Randi Larsen
authors.initials: RL
authors.lastname: Indrevær
authors.forename: Kristine Lillebø
authors.initials: KL
authors.lastname: Holm
authors.forename: Johannes
authors.initials: J
authors.lastname: Landskron
authors.forename: Heidi Kiil
authors.initials: HK
authors.lastname: Blomhoff
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007156:Immunologic Memory / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D015703:Antigens, CD; C092722:CD180 protein, human; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D014212:Tretinoin