The adaptive immune system is compartmentalized into primary and secondary lymphoid organs. In mammals, primary lymphoid organs include the thymus and the bone marrow where immature T cells and B cells develop, respectively. In both tissues, developing lymphocytes undergo RAG-mediated somatic recombination of their antigen receptors followed by several tolerance checkpoints which prevent reactivity to self-antigens. Given the enormous diversity of B cell receptors (BCRs) and T cell receptors (TCRs) generated by the recombination process, the frequency of lymphocytes able to respond to a specific antigen is very low.1 Secondary lymphoid organs (SLOs) provide a structured environment to facilitate interactions between low frequency antigen-specific B and T cells as well as cognate antigen displayed by antigen presenting cells (APCs), resulting in the initiation of effective adaptive immune responses. The spleen is the most evolutionary ancient SLO, being present in all jawed vertebrate lineages.2,3 Generally, splenic cellular organization increases in complexity from the ancient jawed vertebrate lineages, such as cartilaginous fishes, to more recently diverged lineages such as mammals. However, in almost all lineages the spleen contains defined white pulp, where immune cells are primarily located, and red pulp which filters dead and dying red blood cells and helps transport antigens to the white pulp. Embedded within the white pulp are B cell follicles which are bordered by organized T cell zones (eg, mammals) or scattered T cell clusters (eg, cartilaginous fishes).3,4 It is within these B cell follicles that antigen accumulates and is displayed in an intact form, thus maintaining structural epitopes for antigen-specific B cell selection.