Date of Award
Doctor of Philosophy (PhD)
The roles of innate and adaptive immune components are not firmly established for the generation of gut commensal bacteria-specific IgA during homeostasis. To address this, we used flow cytometric sorting of IgA bound in situ to fecal bacteria, a technique that we refined and modified in the lab. In work detailed here, we report that the presence of T cells increased the repertoire of IgA bound bacteria, although a substantial fraction of IgA appears T-independent. Consistent with this, the IgA response was not markedly affected by individual deficiencies in innate pathways upstream of T cell responses such as TLR2, and MyD88, nor the BATF3-dependent CD11b–CD103+ dendritic cell subset. However, lack of TLR4 signaling resulted in diminished IgA to Verrucomicrobiaceae and Lactobacillaceae families, which are known to be associated with anti-inflammatory states. Moreover, mice with dendritic cell-specific deletion of Notch2, which are deficient in the CD11b+CD103+ subset, showed decreased generation of IgA to Bacteroidaceae and Paraprevotellaceae families, but an increase in the IgA bound to pathobionts. Finally, we found that TCR transgenic cells specific to commensal bacteria could induce IgA to bacterial cell-surface antigens upon transfer, and contrary to previous results, we did not observe a strict requirement for the Th17 helper cell subset for IgA induction. Thus, these data support the notion that a specific subset of commensal bacteria can induce T-dependent and T-independent IgA responses that can be modulated by discrete innate immune components.
Chair and Committee
Thaddeus Stappenbeck, Paul Allen, Deepta Bhattacharya, Marco Colonna
Rao, Sindhuja, "Selective Immune Recognition of Gut Commensal Bacteria by Immunoglobulin A" (2016). Arts & Sciences Electronic Theses and Dissertations. 887.
Available for download on Saturday, August 15, 2116