Melanomacrophage Centers As a Histological Indicator of Immune Function in Fish and Other Poikilotherms

Abstract

Melanomacrophage centers (MMCs) are aggregates of highly pigmented phagocytes found primarily in the head kidney and spleen, and occasionally the liver of many vertebrates. Preliminary histological analyses suggested that MMCs are structurally similar to the mammalian germinal center (GC), leading to the hypothesis that the MMC plays a role in the humoral adaptive immune response. For this reason, MMCs are frequently described in the literature as "primitive GCs" or the "evolutionary precursors" to the mammalian GC. However, we argue that this designation may be premature, having been pieced together from mainly descriptive studies in numerous distinct species. This review provides a comprehensive overview of the MMC literature, including a phylogenetic analysis of MMC distribution across vertebrate species. Here, we discuss the current understanding of the MMCs function in immunity and lingering questions. We suggest additional experiments needed to confirm that MMCs serve a GC-like role in fish immunity. Finally, we address the utility of the MMC as a broadly applicable histological indicator of the fish (as well as amphibian and reptilian) immune response in both laboratory and wild populations of both model and non-model vertebrates. We highlight the factors (sex, pollution exposure, stress, stocking density, etc.) that should be considered when using MMCs to study immunity in non-model vertebrates in wild populations.

Keywords: comparative immunology; fish immunology; germinal center; melanomacrophage center; non-model organisms.

Figure 1

Light micrographs of stickleback (Gasterosteus aculeatus) splenic melanomacrophage centers. (A) Unstained spleen at 50×. Scale bar equals 250 µm. Box outlines magnified section in panel (B). (B) Unstained spleen at 200×. Scale bar equals 62.5 µm. (C) H&E-stained spleen at 200×, and black arrows indicate MMCs. Scale bar equals 62.5 µm.

Figure 2

Phylogeny showing melanomacrophage center (MMC) gains and losses across vertebrate species. Detailed phylogenies of fish, amphibian, and reptilian species can be found in Supplemental Material. The phylogeny is not time-calibrated and was plotted using the ape package in R (57), using a topology obtained from the OneZoom database (58). Drawings by Doreen J. Bolnick.