Natural IgM antibodies: from parias to parvenus.

Over the years, natural IgM antibodies were considered as the parias among the immune competent molecules. Their characteristic properties, like low affinity, cross-reactivity and pentameric structure, were assessed as difficult and nebulous. Today, mainly based on the persistent work of a few researchers and the key discoveries on innate immunity, natural IgM antibodies are "back on stage". Their important role in the immune response against invasive particles, modified self-components and altered cells is accepted. All the so far negatively judged features have to be seen in a different light, e.g. low affinity seems to be good for function and does not exclude specificity, cross-reactivity is no longer judged as unspecific, but instead as a very economic way of immune recognition and the pentameric structure is important for binding capacity and functional activities. In addition, with the use of natural IgM antibodies, a new field of tumour-specific targets has been encountered, the carbo-neo-epitopes, which are commonly found on post-transscriptionally modified membrane receptors. Having understood the typical features of natural IgM antibodies, their renaissance opens a new area of cancer therapeutics and diagnostics.