The mammalian gut is colonized by many nonpathogenic, commensal microbes. To prevent the body from mounting inappropriate immune responses to these microbes, plasma cells in the gut produce large amounts of immunoglobulin A (IgA) specific for commensal bacteria. Because of the difficulties of uncoupling IgA production from microbial colonization, how commensal bacteria shape the gut IgA response is not well understood. Hapfelmeier et al. (see the Perspective by Cerutti) have now devised a way to get around this problem by developing a reversible system of gut bacterial colonization in mice. Commensal-specific IgA responses were able to persist for long periods of time in the absence of microbial colonization and required the presence of high microbial loads in the gut for their induction. IgA responses upon bacterial reexposure did not resemble the synergistic prime-boost effect seen in classical immunological memory responses but rather exhibited an additive effect that matched the current bacterial content present in the gut. The body thus constantly adapts the commensal-specific immune response to the microbial species present in the gut, which contrasts with the systemic immune response, which persists in the absence of pathogenic microbes.
S. Hapfelmeier, M. A. E. Lawson, E. Slack, J. K. Kirundi, M. Stoel, M. Heikenwalder, J. Cahenzli, Y. Velykoredko, M. L. Balmer, K. Endt, M. B. Geuking, R. Curtiss 3rd, K. D. McCoy, A. J. Macpherson, Reversible microbial colonization of germ-free mice reveals the dynamics of IgA immune responses. Science 328, 1705–1709 (2010). [Abstract] [Full Text]