Microbial induction of B and T cell areas in rabbit appendix.

Gut-associated lymphoid tissue (GALT) development requires interaction with the intestinal microbiota. Because murine secondary lymphoid tissue development is driven by positive feedback interactions between B cells and stromal cells, we used in situ hybridization to determine whether intestinal commensals influence such interactions during rabbit appendix development. The features of positive feedback interactions we examined (CXCL13 mRNA expression, B cell accumulation and FDC differentiation) increased during early follicle development, but stalled in the absence of intestinal commensals. These features were reinitiated by commensals that stimulated follicle development and intrafollicular B cell proliferation. Our results suggest that rabbit appendix follicles develop in two phases: an initial phase of B cell recruitment to nascent follicles, possibly through positive feedback interactions, and a subsequent phase of intrafollicular B cell proliferation stimulated by intestinal commensals. In addition, we found that intestinal commensals stimulate appendix CCL21 mRNA expression and T cell area formation.