Browsing School, Graduate by Title "Ontogeny and Phylogeny of the Splenic White Pulp"
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Ontogeny and Phylogeny of the Splenic White PulpSecondary lymphoid organs (SLO) provide the structural framework for the co-concentration of antigen and lymphocytes required for an efficient adaptive immune response. The spleen is the primordial SLO, and evolved concomitantly with Ig-/TCR:pMHC-based adaptive immunity. The ontogeny of the spleen's lymphoid compartment, the white pulp (WP), begins in all characterized vertebrates with an accumulation of B cells around splenic vasculature. In the mature WP of the amphibian Xenopus laevis and the shark Ginglymostoma cirratum, B cells retain the ancestral vasculature-associated feature and neither species supports the formation of GC, though class switch recombination and somatic hypermutation occur in Xenopus B cells. In order to gain insight into the development and evolution of vertebrate SLO we proposed three distinct approaches to determine the level of evolutionary conservation in WP ontogeny and microarchitecture, establish the multiplicity of DC lineages in the Xenopus spleen, and identify the initiating subset of B cells in mammalian WP ontogeny. We show that perivascular accumulation of B cells marks the onset of WP ontogeny in Xenopus (as we have previously demonstrated in nurse shark), demonstrating that the ontogeny of the WP is conserved, while displacement of the FO by the PALS is a recently evolved characteristic of the mammalian splenic WP. Further, we show that the Xenopus XL cells express high levels of MHC Class II, suggestive of a conventional hematopoietic lineage. Upon immunization, XL cells reposition themselves at the internal perimeter of the FO, acquire and retain native antigen at their plasma membrane, and express CXCL13 and BAFF, suggesting an FDC-like function, and therefore that XL cells perform "double duty," presenting Ag to both T cells and B cells. Lastly, we show that, in the mouse, WP ontogeny is initiated at birth by transitional B cells, likely of the B-1a lineage, upon acquisition of chemotactic responsiveness to the B cell chemoattractant CXCL13, which is produced by embryonic pre-FDC prior to the onset of WP ontogeny. These studies demonstrate a progressive accumulation of splenic WP complexity and functionality over the course of vertebrate evolution, and provide insight into the regulation of lymphoid ontogeny, both developmental and pathological.