The evolution of affinity maturation: Germinal center-like cell aggregates in fish (81.16)

Abstract

Abstract Compared with mammals, fish and amphibians have a limited antibody affinity maturation response, an outcome attributed to their lacking distinguishable germinal centres. There is evidence of Ig hypermutation and antigen driven selection, and as such we'd anticipate some sort of germinal center (GC)-like structures, perhaps akin to the varied GC-like cell aggregates observed in different human autoimmune disease. To establish whether fish have GC-like cell aggregates we did in situ hybridization and laser capture microscopy coupled with gene expression analyses on spleen sections of BSA immunized channel catfish. AID expressing cells were found predominantly in tight association with so called melano-macrophage centers or clusters (MMCs). Melano-macrophages have previously been noted for their ability to capture and retain whole antigen and thus had been proposed to be functionally analogous to follicular dendritic cells. Though far smaller than mammalian GCs the fish MMCs also contain CD4 expressing cells and a few flanking plasma cells. However TUNEL assays did not reveal the expected numbers of surrounding apoptotic cells. While there are alternative theories as to the function of these cell aggregates we are proposing that they are primitive germinal centers. Funded by the National Science and Engineering Research Council - Canada