title: Stimulation of Toll-Like Receptors profoundly influences the titer of polyreactive antibodies in the circulation.
abstract: Polyreactive antibodies are a major component of the natural antibody repertoire and bind to a variety of structurally unrelated molecules. These antibodies are thought to provide a first line of defense against bacterial infections and play a major role in the clearance of apoptotic cells. What triggers the secretion of these antibodies has remained an enigma. Using a surrogate assay for measuring polyreactive antibodies, we found that about 50% of serum IgM is polyreactive and that stimulation of TLR4(+/+), but not TLR4(-/-), mice resulted in a 40 fold increase in polyreactive antibodies. Stimulation of TLRs 3, 7, 9 also increased the secretion of polyreactive antibodies. Infection with a virus or tissue damage induced by a toxin similarly led to an increase in polyreactive antibodies in MyD88(+/+), but not MyD88(-/-) mice. We conclude that stimulation of TLRs is a key link in the mechanism of polyreactive antibody secretion into the circulation.
authors.affiliation: Experimental Medicine Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Sreenivasulu
authors.initials: S
authors.lastname: Gunti
authors.affiliation: Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Messer
authors.affiliation: Pharmacology Section, Laboratory of Bacterial Genetics, National institutes of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
authors.forename: Chengfu
authors.initials: C
authors.lastname: Xu
authors.affiliation: Pharmacology Section, Laboratory of Bacterial Genetics, National institutes of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.affiliation: Pharmacology Section, Laboratory of Bacterial Genetics, National institutes of Diabetes and Digestive and Kidney Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Coleman
authors.affiliation: Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
authors.forename: Karin E
authors.initials: KE
authors.lastname: Peterson
authors.affiliation: Laboratory of Persistent Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Hasenkrug
authors.affiliation: Experimental Medicine Section, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research, National institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Abner L
authors.initials: AL
authors.lastname: Notkins
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D051193:Toll-Like Receptors / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001323:Autoantibodies; D051193:Toll-Like Receptors