IgM antibodies exist both in a pentameric soluble form and as membrane-bound monomers mainly on the surface of naïve B cells, where they are part of the antigen receptor complex. Naïve B cells, constituting 75% of the peripheral blood B cell repertoire in humans (Klein et al., 1997), contain the largest diversity of an individual's rearranged immunoglobulin genes. The naturally occurring antibody repertoire contains specific antibodies against various antigens. In a primary immune response, B cells expressing antigen-specific IgM molecules are activated and differentiate into antibody-producing and -secreting plasma cells. Secreted antigen-specific IgM molecules are the first immunoglobulins occurring during a primary immune response. On the other hand, so-called natural antibodies exist independently of antigenic stimulation and are thought to contribute to the first line of defense against infections (Carsetti et al., 2004; Ochsenbein & Zinkernagel, 2000) as well as malignancy (Brändlein et al., 2003).

In addition to antibody-secreting plasma cells, memory B cells are generated during a primary immune response, a process that includes somatic hypermutation in the germinal centers. Most of the memory B cells have undergone a class switch and do not express IgM. In humans, however, IgM molecules with somatic mutations have been identified (Van Es et al., 1992). These somatically mutated IgM molecules contribute to an individual's immunological memory and constitute about 10% of the total peripheral blood B cell repertoire (Klein et al., 1997). IgM-expressing memory B cells protect against infections by encapsulated bacteria, and develop during the first year of life (Kruetzmann et al., 2003).