Secretion of Polyreactive Antibodies is Profoundly Influenced by the Stimulation of Toll-Like Receptors (TLR)

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NIDCR	IMMUNO-17

Authors

• G Sreenivasulu
• RJ Messer
• C Xu
• KJ Hasenkrug
• WG Jr Coleman
• AL Notkins

Abstract

Polyreactive antibodies are a major component of the natural antibody repertoire and are capable of binding to a variety of structurally unrelated antigens. 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. However, what triggers the production of these antibodies and their release into the circulation has remained an enigma. In the current study we developed an assay for measuring polyreactive antibodies and with this assay showed that the stimulation of TLRs, particularly TLR4, in C57BL/6 mice resulted in a 30 fold increase in polyreactive antibody, whereas the same experiment performed in TLR4 KO or Myd88 KO mice resulted in only a minimal increase in polyreactive antibodies. Stimulation of TLRs 3, 7 and 9 also resulted in a significant, but lesser, increase in polyreactive antibodies than occurred with TLR4. Infection of mice with lactate dehydrogenase virus (a high titer RNA virus) or liver damage induced by carbon tetrachloride also significantly increased polyreactive antibodies. Based on these findings we conclude that the level of polyreactive antibody in the circulation is profoundly influenced by the stimulation of TLRs.

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