Editors' ChoiceImmunology

The persistent life of IgA

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Science Translational Medicine  29 Jul 2015:
Vol. 7, Issue 298, pp. 298ec129
DOI: 10.1126/scitranslmed.aac9740

When we first learn about antibodies in an intro immunology course, immunoglobulin A (IgA) is always classified as being the dominant isotype in the mucosal immune system. However, we are far from a complete understanding of its contribution to mucosal immunity. In some contexts, IgA helps protect the host from infection, but much remains to be discovered on the functional role of IgA in the interactions between the commensal microbiota and host physiology beyond an increase in germ-free mice after colonization with commensal microbes. To gain insight into this IgA-mediated host microbe crosstalk, Lindner et al. used next-generation sequencing to characterize the IgA repertoire in gnotobiotic mice either monocolonized with one of several gut microbes or with a community of microbes from specific pathogen free (SPF) mice. Unsurprisingly, these experiments showed that increasing gut microbial community complexity led to an increase in IgA repertoire diversity. Notably, different gnotobiotic mice colonized with the same microbe had nonoverlapping IgA repertoires. Therefore, the bulk of the IgA repertoire analyses were performed longitudinally from small intestine biopsies with each animal serving as its own control.

Using this longitudinal study design, the authors performed a series of comparisons and microbiome perturbations in gnotobiotic animals. They found that longitudinal samples from animals maintained with the same microbiota yielded a strong overlap in their repertoire composition over 4 weeks. There was also a strong overlap in the IgA repertoire between Peyer’s patch memory B cells, IgA-secreting plasma cells in the gut, and mammary glands. In a microbiota perturbation experiment, gnotobiotic mice were initially monocolonized and subsequently colonized with the community from an SPF mouse. As expected, their second colonization led to an increase in IgA repertoire diversity. However, even in the context of this large increase in microbiota complexity, a proportion of the original IgA repertoire overlapped with the repertoire post-SPF colonization, suggesting that memory of prior colonization events is maintained even after large perturbations, at least in the time frame of their experiment. Even more surprising, the authors found a stable IgA repertoire, longitudinally within each mouse, before and after four weeks of antibiotic treatment. Importantly, the authors found similar results in human subjects, suggesting that the exciting new insights into IgA diversity and persistence in the controlled gnotobiotic environment parallel those in humans, opening the possibility for many new translational discoveries into IgA diversity, persistence, and function.

C. Lindner et al., Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Nat. Immunol. 10.1038/ni.3213 (2015). [Abstract]

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