Lymphoid tissues have a unique role in the organization and function of the adaptive immune system. Mechanisms driving the development of these tissues have fascinated immunologists for the last 175 years. In this review, we will initially focus on historical literature describing lymph node (LN) anlage development and then on the contemporary understanding of the molecular mechanisms driving LN and Peyer's patch (PP) formation. Utilizing transgenic reporters and gene knockout mice, the interplay between hematopoietic inducer cells and stromal organizer cells has been shown to have a key role in the development and organization of the lymphoid tissues. Although PPs and LNs share many similarities in their development, key differences in the molecular requirements for their development have recently emerged.
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