Immunoglobulin A Antibody Composition Is Sculpted to Bind the Self Gut Microbiome

ABSTRACT Despite being the most abundantly secreted immunoglobulin isotype, the reactivity of IgA antibodies towards each individual’s own gut commensal bacteria still remains elusive. By colonizing germ-free mice with defined commensal bacteria, we found the binding specificity of bulk fecal and serum IgA towards resident gut bacteria resolves well at the species level and has modest strain level specificity. IgA hybridomas generated from lamina propria B cells of gnotobiotic mice showed that most IgA clones recognized a single bacterial species, while a small portion displayed polyreactivity. Species-specific IgAs had a range of strain specificities. Given the unique bacterial species and strain composition in each individual’s gut, our findings suggest the IgA repertoire is uniquely shaped to bind our self gut bacteria.