Much has been learned about the structure, function, and production of IgM, since
the antibody's initial characterization. It is widely accepted that IgM provides a
first line of defense during microbial infections, prior to the generation of adaptive,
high-affinity IgG responses that are important for long-lived immunity and immunological
memory. Although IgM responses are commonly used as a measure of exposure to infectious
diseases, it is perhaps surprising that the role of and requirement for IgM in many
microbial infections has not been well explored in vivo. This is in part due to the
lack of capabilities, until relatively recently, to evaluate the requirement for IgM
in the absence of coincident IgG responses. Such evaluations are now possible, using
gene-targeted mouse strains that produce only IgM, or isotype-switched IgG. A number
of studies have revealed that IgM, produced either innately, or in response to antigen
challenge, plays an important and perhaps under appreciated role in many microbial
infections. Moreover, the characterization of the roles of various B cell subsets,
in the production of IgM, and in host defense, has revealed important and divergent
roles for B-1a and B-1b cells. This review will highlight studies in which IgM, in
its own right, has been found to play an important role, not only in early immunity,
but also in long-term protection, against a variety of microbial pathogens. Observations
that long-lived IgM responses can be generated in vivo suggest that it may be feasible
to target IgM production as part of vaccination strategies.