Stimulation of Toll-Like Receptors profoundly influences the titer of polyreactive antibodies in the circulation.

Sreenivasulu Gunti,William G Coleman,Ronald J Messer,Karin E Peterson,Abner L Notkins,Ming Yan,Chengfu Xu,Kim J Hasenkrug

doi:10.1038/srep15066

Sreenivasulu Gunti, William G Coleman + Show 6 more

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https://doi.org/10.1038/srep15066

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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.

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Many of which show different binding patterns and affinities when evaluated with a large panel of antigens
Since it is well known that stimulation of TLR4 with LPS results in a substantial increase in serum immunoglobulins[16], we looked for such an increase after injection of LPS
The work reported here shows that Toll-Like Receptors (TLRs) play a critical role in the secretion of polyreactive antibodies

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Many of which show different binding patterns and affinities when evaluated with a large panel of antigens. To develop an assay for measuring polyreactive antibodies, we chose a synthetic molecule , dinitrophenol (DNP), which is not present in the environment and to which the host would not be exposed. Antibodies in the serum that react with DNP would almost certainly be polyreactive. Unanswered, is what triggers the secretion of polyreactive antibodies that are present in normal sera. Because of the low affinity of polyreactive antibodies, it is unlikely that stimulation by one or more of the serum antigens which might bind to polyreactive B cell receptors, would provide a strong enough signal to result in the secretion of polyreactive antibodies. We hypothesized that the stimulation of Toll-Like Receptors (TLRs) on B lymphocytes, by their respective agonists, would provide strong enough stimuli to trigger the secretion of polyreactive antibodies into serum.

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