IgM in microbial infections: taken for granted?

Abstract

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.

Figure 1. Possible mechanisms that would support long-term maintenance of IgM

Four non-mutually exclusive sources of long-lived IgM responses during microbial infection are proposed (from top left, clockwise). 1) Newly formed naive cells, upon encounter with chronic antigen or persistent infection, may differentiate into IgM-secreting cells, 2) Natural antibody-producing cells may provide a continuous source of pathogen-specific polyreactive IgM, 3) Memory B-1b cells elicited during primary infection may serve as a source of IgM following antigen re-exposure, 4) Long-term IgM-secreting plasmablasts or plasma cells may maintain production of IgM in the spleen extrafollicular regions or the bone marrow. Ag: antigen; Ab: antibody.