The melanomacrophage center is a potential evolutionary precursor to the mammalian germinal center

Abstract

Abstract The melanomacrophage center (MMC), aggregates of highly pigmented melanomacrophages found within the lymphoid tissues of ectotherm vertebrates, is thought to be the evolutionary precursor to the mammalian germinal center (GC). Studies of cold-blooded vertebrates suggest that the MMC is the site of the humoral adaptive immune response, where B cells proliferate, generate high affinity antibody, and undergo affinity maturation. MMCs transiently increase in size/number following immunization or bacterial infection, supporting the hypothesis that the MMC response is likely linked to the adaptive immune response. However, while morphological studies and shared expression of a GC specific gene further support the idea that the MMC is a proto-GC, melanomacrophages perform many functions not associated with the humoral adaptive immune response. Therefore, to determine if the MMC is serving in a GC-like capacity or is a more generalist feature of ectotherm biology, we turned to the fish model system, three spine stickleback. Fish MMCs increase in size in response to immunization with NP-CGG in alum, but not control injection with adjuvant alone. Fish MMCs are also found in close proximity to lymphocytes and cells expressing the B/T cell activation marker GL7. These preliminary studies not only give further support to the notion of the MMC as a GC homolog, but also provide important tools to broaden the study of adaptive immunity in other fish, reptilian, and amphibian systems.