Isolated lymphoid follicles (ILFs)³ are organized intestinal lymphoid structures, whose formation can be induced by luminal stimuli. ILFs have been demonstrated to act as inductive sites for the generation of immune responses directed toward luminal stimuli, however the phenotype of the immune response initiated within ILFs is largely uninvestigated. In order to gain a better understanding of the immune responses initiated within ILFs, we examined phenotypic and functional aspects of the largest cellular component of the murine ILF lymphocyte population, B-lymphocytes. We observed that murine ILF B-lymphocytes are comprised of a relatively homogenous population of follicular B-2 B-lymphocytes. Consistent with their proximity to multiple stimuli, ILF B-lymphocytes displayed a more activated phenotype when compared with their counterparts in the spleen and Peyer's patch (PP). ILF B-lymphocytes also expressed higher levels of the immunomodulatory B7 and CD28 family members B7X and PD1 when compared with their counterparts in the spleen and PP. ILF B-lymphocytes preferentially differentiate into IgA producing plasma cells, and produce more IL-4 and IL-10 and less IFN when compared with their counterparts in the spleen. Immunoglobulin repertoire analysis from individual ILFs demonstrated that ILFs contain a polyclonal population of B-lymphocytes. These findings indicate that murine ILFs contain a polyclonal population of follicular B-2 B-lymphocytes with a phenotype similar to PP B-lymphocytes, and that in unchallenged animals, ILFs promote immune responses with a homeostatic phenotype.