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: Sreenivasulu Gunti, Ronald J Messer, Chengfu Xu, Ming Yan, William G Coleman Jr, Karin E Peterson, Kim J Hasenkrug, Abner L Notkins
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 15066 (Oct 14 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26463758 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Autoantibodies
• Toll-Like Receptors

Topics

• Animals
• Autoantibodies (blood, immunology)
• Female
• Immunity, Innate (immunology)
• Immunization (methods)
• Mice
• Mice, Inbred C57BL
• Toll-Like Receptors (immunology)
• Up-Regulation (immunology)