title: A distinct Toll-like receptor repertoire in human tonsillar B cells, directly activated by PamCSK, R-837 and CpG-2006 stimulation.
abstract: Toll-like receptors (TLRs) recognize specific pathogen-associated molecular patterns (PAMPs), which subsequently trigger innate immunity. Recent data also suggest a role for TLRs in the direct activation of adaptive immune cells. In the present study, the expression and function of TLR1-TLR10 were characterized in purified human tonsillar B cells, focusing on differences among CD19+ CD38- CD27- (naïve B cells), CD19+ IgD- CD27-[germinal centre (GC) B cells] and CD19+ CD38- CD27+ (memory B cells) cells. The study was also designed to compare the TLR expression in B cells obtained from infected and hyperplastic tonsils that served as controls. The results demonstrated a distinct repertoire of TLRs, in which TLR1, TLR2, TLR7, TLR9 and TLR10 predominated. No differences were found among naïve, GC and memory B cells. Tonsillar infection did not substantially alter the TLR expression profile in ex vivo-isolated B-cell subsets. Purified CD19+ B cells stimulated with Pam3CSK4, R-837 and CpG oligodeoxynucleotide (ODN) 2006, via TLR1/TLR2, TLR7 and TLR9, respectively, showed an induction of interleukin-6 secretion and an up-regulated expression of human leucocyte antigen (HLA)-DR. Collectively, the present study demonstrates that B cells exhibit constitutively high levels of specific TLRs, which are not developmentally regulated during the B-cell differentiation process. Ongoing microbial infections, such as chronic tonsillitis, do not appear to affect the TLR profile in B cells. Furthermore, the distinct expression of TLRs allows B cells to respond directly to the cognate PAMPs. This further emphasizes the role of TLRs in directly activating adaptive immune cells.
authors.affiliation: Laboratory of Clinical and Experimental Allergy Research, Department of Otorhinolaryngology, Malmö University Hospital, Lund University, Sweden. anne.mansson@med.lu.se
authors.forename: Anne
authors.initials: A
authors.lastname: Månsson
authors.forename: Mikael
authors.initials: M
authors.lastname: Adner
authors.forename: Ulf
authors.initials: U
authors.lastname: Höckerfelt
authors.forename: Lars-Olaf
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D002352:Carrier Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry / Q000379:methods; D018858:Germinal Center / Q000276:immunology; D006801:Humans; D000077271:Imiquimod; D007150:Immunohistochemistry / Q000379:methods; D007156:Immunologic Memory; D015850:Interleukin-6 / Q000276:immunology; D008213:Lymphocyte Activation; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014066:Palatine Tonsil / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051194:Toll-Like Receptor 1 / Q000032:analysis; D051201:Toll-Like Receptor 10 / Q000032:analysis; D051195:Toll-Like Receptor 2 / Q000032:analysis; D051196:Toll-Like Receptor 3 / Q000032:analysis; D051197:Toll-Like Receptor 4 / Q000032:analysis; D051198:Toll-Like Receptor 5 / Q000032:analysis; D051199:Toll-Like Receptor 7 / Q000032:analysis; D051200:Toll-Like Receptor 8 / Q000032:analysis; D051217:Toll-Like Receptor 9 / Q000032:analysis; D051193:Toll-Like Receptors / Q000032:analysis*; D014069:Tonsillitis / Q000276:immunology*
chemical_list: D000634:Aminoquinolines; D002352:Carrier Proteins; C513533:CpG ODN 2006; D015850:Interleukin-6; D009838:Oligodeoxyribonucleotides; C499841:PAM2-Cys-SKKK; D051194:Toll-Like Receptor 1; D051201:Toll-Like Receptor 10; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D000077271:Imiquimod