Antibody specificities are Gut reactions

Germ-free (GF) mice have undeveloped immune systems and practically no antibodies.  How do microbes in the gut (gastro-intestinal tract) stimulate immunity?  This group looked at the specificity of antibodies that develop after GF mice are colonized by individual bacterial species and strains (monocolonization).  They used 8 strains of bacteria to inoculate GF mice and, after 3 weeks, analyzed the specificity of antibodies produced in the gut (recovered from fecal matter) and blood, focusing on the IgA isotype that protects mucosal surfaces.  

Not surprisingly, the antibodies tend to bind specifically to those strains of microbes against which they were stimulated (shown, Figure 1, panel A). They also found that mice monocolonized from birth produce more IgA reactive with that species (termed ‘self’) than newly-introduced species. They make a point about IgA being able to ‘aggregate pathogenic bacteria’ and ‘selectively coat disease-associated bacteria’ but it is unclear how IgA itself could distinguish dangerous from benign and anyway they tested only benign bacteria.  

A small panel (29) of monoclonal IgA antibodies cloned from gut tissues of monocolonized mice also showed species specificity. Finally, they showed that monoclonal IgA antibodies with specific binding activity could be detected in the feces of mice that had been force-fed the IgA 3 hours previously, suggesting a targeted, potential therapy (e.g., against the human pathogen Clostridioides difficile). 

Yang C, Chen-Liaw A, Spindler MP, Tortorella D, Moran TM, Cerutti A, Faith JJ. Immunoglobulin A antibody composition is sculpted to bind the self gut microbiome. ScienceImmunology. 2022 Jul 15;7(73)