Hexameric immunoglobulin M in humans: Desired or unwanted?

Abstract

Immunoglobulin M (IgM) is the first antibody produced upon infection, and is often suggested as the first line of defense of human immune system. In addition to being present on the surface of naive B cells as a monomeric molecule, IgM is always secreted as a polymer. The most abundant IgM polymer in humans is pentamer, composed of five monomeric units, joined together by so-called joining on chain. On the other hand, it is well known that hexameric IgM can be also found in human sera. Its presence is often related to different dissorders (Waldenstrom's macroglobulinemia, cold agglutinin, and recurrent urinary bacterial infections), although it is believed that small amounts of hexamer are present in normal human sera as well. Unlike pentamer, IgM hexamer contains six monomeric blocks and completely lacks J chain. Although it has been decades since its discovery, the precise function of IgM hexamer is still unknown. Since it was documented that hexamer is very potent in activating complement, it is suggested that its production in humans must be under strict control, and that it is produced in special conditions, when strong activation of complement is absolutely needed. However, the question is whether hexameric IgM is really a secret weapon or just an undesirable molecule in humans. According to structural and known functional characteristics of both pentamers and hexamers of IgM, it can be concluded that hexamers are, in addition to being maybe too reactive to be around, probably not that efficient in protecting us from bacterial and viral infections. (C) 2011 Elsevier Ltd. All rights reserved.