Regulation of gut microbiota-specific IgA by TFR cells 3801

Description IgA is the predominant antibody at mucosal surfaces, playing a critical role in intestinal defense and regulation of commensal bacteria. About one-third of commensal bacteria are coated by IgA in healthy humans. IgA responses can be polyreactive with low affinity or highly specific with high affinity. T follicular helper (TFH) cells support the production of high-affinity IgA. T follicular regulatory (TFR) cells also regulate antibody responses; however, their role in regulating IgA responses to gut commensals remains unclear. We hypothesized that TFR cells suppress high-affinity IgA responses to gut commensals through specific suppressive pathways. Using a TFR-deficient mouse model (Bcl6-fl/fl Foxp3-cre, Bcl6FC), we found comparable total microbiomes between control and Bcl6FC mice via 16S sequencing, but with increased diversity in the IgA-coated (IgA+) microbiome of Bcl6FC mice. Select taxa from Clostridia, Prevotellaceae, and Desulfovibrionaceae showed higher relative abundance and IgA-Coating Index (ICI) scores in IgA+ fraction of Bcl6FC mice, indicating increased IgA binding to these taxa. Following food allergy induction, Bcl6FC mice showed heightened and sustained IgA binding to commensals, which was normalized by restoring TFR cells. We are currently probing how TFR cells regulate IgA specificity for gut bacteria while exploring specific suppressive pathways used by TFR cells to regulate IgA specificity and affinity during homeostasis versus inflammation in the gut. Funding Sources R21AI176762 and T32 AI060519 Topic Categories Mucosal and Regional Immunology (MUC)