The acquisition of narrow binding specificity by polyspecific natural IgM antibodies in a semi‐physiological environment

Abstract

Natural IgM Abs play an important role in clearing pathogens and preventing autoimmunity. The molecular mechanisms that mediate these processes are understood only to a limited degree. This shortcoming is largely due to the fact that isolated natural IgM Abs commonly recognize a variety of unrelated antigens (Ags). Such polyspecificity is generally believed to be an inherent property of natural Abs. However, there is increasing evidence that it may be induced by non‐physiological binding conditions. In this study, we compared the specificity of natural IgM Abs in conventional buffers and undiluted sera deficient in immunoglobulins. All tested Abs were found to lose their polyspecificity in the serum environment. When in serum, the Abs no longer reacted with conventional screening Ags, including hapten‐BSA conjugates, ssDNA, thyroglobulin and myosin, but fully retained their reactivity with specific peptide Ags selected from a phage display library. The acquisition by IgM of narrow binding specificity was also observed when muscle tissue sections were used as a source of endogenous Ags. The loss of polyspecificity by different Abs was dependent on the presence of different serum constituents. The results from this study suggest that the seemingly inherent polyspecificity of natural IgM Abs is largely an in vitro phenomenon related to the lack of normal blood components in the medium.