Perspectives on antigen presenting cells in zebrafish

Abstract

Antigen presentation is a critical step in the activation of naïve T lymphocytes. In mammals, dendritic cells (DCs), macrophages, and B lymphocytes can all function as antigen presenting cells (APCs). Although APCs have been identified in zebrafish, it is unclear if they fulfill similar roles in the initiation of adaptive immunity. Here we review the characterization of zebrafish macrophages, DCs, and B cells and evidence of their function as true APCs. Finally, we discuss the conservation of APC activity in vertebrates and the use of zebrafish to provide a new perspective on the evolution of these functions.

Keywords: Antigen-presenting cells; B lymphocytes; Dendritic cells; Macrophages; Zebrafish.

Fig. 1

Morphological characterization of zebrafish DCs. PNA^hi DC-like cells, macrophages (mac), monocytes (mono), neutrophils (neu), eosinophils (eos), and mast cells (mast) were isolated from zebrafish kidney marrow. Images originally published in Lugo-Villarino et al. (2010). (A) (Upper) Large dendrites are apparent on DC-like cells by Wright–Giemsa (WG) staining. DC-like cells contain small, acid phosphate (AP)-positive granules, seen as a magenta precipitate. DC-like cells also stain weakly for α-naphthyl acetate esterase (NAE), and are not stained by myeloperoxidase (MPX), periodic acid-Schiff reagent (PAS), and toluidine blue (TB). (Lower) Characteristic black precipitate is visible in the cytoplasm of monocytes by AP staining. Neutrophils, eosinophils, and mast cells all stain strongly for MPX (brown precipitate), PAS (red precipitate), and TB (purple precipitate). (B) Ultrastructure of (Upper) PNA^hi myelomonocytes and (Lower) other leukocytes by TEM. Nucleus (N).

Fig. 2

Expression of the mhc2dab:eGFP (MHC class II) and cd45:DsRed (CD45) transgenes in the adult zebrafish. Immunohistochemistry staining of paraffin sections through the adult zebrafish (A) intestine and (B) brain in double transgenic mhc2dab:eGFP; cd45:DsRed animals. Sections were stained with anti-GFP (green) and anti-DsRed (red) antibodies. Nuclei are stained with DAPI (blue). Lamina propria (LP); lumen (L). DsRed⁺ cells are expected to be T cells and/or neutrophils; eGFP⁺ cells are expected to be B cells; eGFP⁺dsRed⁺ cells (yellow) are expected to be macrophages and/or dendritic cells. Sections were imaged by confocal microscopy and scale bars are shown.