Metabolic depot for nucleated erythrocyte degradation: molecular and structural elucidation of the teleost melanomacrophage center
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Zhengyang Zhou,
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Jinlai Gu,
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Jie He,
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Jun Wang,
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Zhengdong Zhong,
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Quanxin Xiong,
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Min Qi,
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Shen Lian,
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Zhengran Jian,
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Yuanchang Gao,
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Linfeng Kuang,
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Chengwang Lu,
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Shangjie Bai,
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Mingzhu Liu,
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pengfei Li,
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Qing Yu,
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Gaoxue Wang,
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Fei Ling,
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Jorge Galindo-Villegas,
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Tao Liu
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Abstract
The function of melanomacrophage centers (MMCs) has long been controversial. While their foundational function is widely accepted as “metabolic dumps” for waste processing, a widely circulated hypothesis posits that they are primitive germinal centers (GCs) executing adaptive immunity. To elucidate this controversy, this study systematically evaluated the splenic MMCs in a higher teleost (Micropterus salmoides) by combining transmission electron microscopy and high-resolution spatial transcriptomics. Structurally, TEM revealed that the MMC comprises a core with characteristic sparse cellular density, filled with cellular debris and encapsulated by a fibrous layer. Molecularly, under physiological conditions, MMC regions exhibited low transcriptional activity. We did not detect clear enrichment of B cell and T cell lineage genes, and the key GC marker aicda was not observed. Conversely, its predominant molecular signature was characterized by macrophage-driven iron metabolism (e.g., ferritin) and erythrocyte degradation (e.g., hba1). Furthermore, the physicochemical properties of MMC pigments (e.g., argyrophilia) suggest that traditional histological staining methods warrant cautious interpretation regarding potential non-specific signals. In conclusion, our findings characterize the MMC as a highly specialized metabolic processing and sequestration niche. This study provides new perspectives on the evolution of immune-metabolic homeostasis in poikilothermic vertebrates, advances comparative immunology, and offers a critical scientific reference for the accurate interpretation of MMCs as a biological indicator in pathology and ecotoxicology.
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