Immunoglobulin A (IgA) is a prominent, widely distributed antibody that plays a critical role in host defense and immune function. Over 80% of all human plasma cells produce IgA and are found in the intestinal mucosa. Research has historically focused on IgA’s role in immunity against pathogenic organisms, but less is known about its equally important role in maintaining intestinal homeostasis. Investigators in this study sought to better characterize the mechanisms through which IgA selects and binds commensal bacteria, and the resulting implications for humoral immunity.
A new approach was taken by researchers who used flow cytometry and gene sequencing in immunodeficient mouse models to identify commensal IgA targets (JJ Bunker at al., Immunity. 2015 Sep 15;43(3):541-53) . They also sought to understanding the contribution of T cell activation to these pathways, as well as which B cell lineages contribute to bacterial coating. Their investigations yielded a number of interesting insights. First, they found that anatomical location, rather than bacterial identity, was the primary determinant in eliciting an IgA response. Antibody coating was localized to the small intestine rather than the colon, perhaps because of the collections of lymphoid tissues in this portion of the gastrointestinal tract that allow for priming of plasma cells in response to antigen exposure. Next, they studied mice lacking T cells, and surprisingly found that bacterial targeting and coating was a T-cell independent process. There were, however, two bacterial species that evaded these T-cell independent responses and required T cell activation for coating. Finally, researchers investigated different B cell lineages, and showed that a poorly understood B cell subtype, B1b, is indeed specialized to produce T cell independent IgA responses to commensal bacteria. They also found the main contributor to free intestinal IgA was B2 B cells, rather than B1a cells that was suggested by prior research.
The collection of investigations outlined in this paper contributed an important advancement to our understanding of IgA development and response to commensal intestinal bacteria. As IgA is known to play an important role in microbiota-associated disease, such as inflammatory bowel disease, characterizing these pathways lays an important foundation for identifying therapeutic interventions in the future.