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Adaptive immune responses are induced within secondary lymphoid organs (SLOs) such as lymph nodes, spleen and Peyer’s patches. Structure and compartmentalization of SLOs is determined by fibroblastic stromal cells which built and maintain specialized microenvironments for T cell or B cell activation. Protective immune responses at sites of high vulnerability require rapid production of immune effector molecules to contain pathogens and to prevent infection of internal organs. Guarding the peritoneal cavity from microbial contaminants that have escaped from the intestine necessitates particularly fast immune reactions to achieve inactivation of toxins and neutralization of pathogens. Non-classical SLOs in the omentum, also known as “milky spots”, function as immune surveillance hubs of the peritoneum. Interestingly, although stromal cells have been identified as the major cell population that foster B cell activation in milky spots and the peritoneal cavity, their identity and functional capacity have remained unknown. Moreover, it is not known whether and to which extent fibroblastic stromal cells impact on macrophages and other myeloid cells that are the highly abundant in the omentum. In order to assess the function of fibroblastic stromal cells in vivo, our laboratory has developed mouse models that facilitate genetic labeling of fibroblastic stromal cells in vivo and to study their function through targeted gene ablation.