MATURATION of the AVIAN IgA SYSTEM CRITICALLY DEPENDS on MICROBIAL COLONIZATION

The avian immune system shows striking differences to its mammalian counterpart such as the complete lack of lymph nodes and the development of B-cells in a unique gut associated lymphoid organ the bursa of Fabricius. At present, little is known about relevance of microbial colonization for the development of the mucosal immune system in birds. In order to address this question, we raised germ free chickens and reconstituted them with the E.coli strain Nissle alone or in combination with an Enterococcus, Lactobacillus and Clostridium strain. Analysis of GALT structures and mucosal immune cell populations revealed no impact of the microbiota on bursal development but a significant role in the development of the mucosal secondary immune organs. Most strikingly, germ free birds completely lacked IgA plasma cells in the lamina propria, systemic and mucosal IgA production and germinal center formation in the caecal tonsils, the most prominent GALT structure in birds. Mono-reconstitution with E.coli Nissle only partially reverted this phenotype but induced a significant IgA response to this bacterium. Tetra-reconstitution further improved but did not fully mature the mucosal immune system as compared with the status in SPF birds. The striking IgA deficiency in germ free birds was paralleled by significantly reduced expression levels of J-chain, AID, BAFF, BAFF-R and poly-IgR mRNAs. We conclude that maturation signals seem to be identical in mammals and birds further supporting the importance of the IgA system in tissue homeostasis which has been conserved for more than 300 million years since birds and mammals segregated.