Anatomy of germinal centers in mouse spleen, with special reference to \u27follicular dendritic cells\u27

Abstract

Lymphocyte proliferation in germinal centers (GC\u27s) is thought to be triggered by antigen retained extracellularly on the surface of special \u27dendritic\u27 cells. The anatomy and function of these cells have not been studied directly or in detail. We therefore examined mouse spleen GC\u27s developing in response to sheep erythrocyte stimulation. We found that distinctive \u27follicular dendritic cells\u27 (FDC\u27s) were present in both the GC and adjacent mantle region of secondary follicles. The large, irregularly shaped nucleus, containing little heterochromatin, allowed for the light microscope (LM) identification of FDC\u27s. By EM, the cell was stellate in shape sending out long, thin sheets of cytoplasm which could fold and coil into complex arrays. The processes were coated extracellularly by an amorphous electron-dense material of varying thickness, as well as particulates including variable numbers of virions. The FDC cytoplasm lacked organelles of active secretory and endocytic cells, such as well-developed rough endoplasmic reticulum (RER) and lysosomes. These anatomical features readily distinguished FDC\u27s from other cell types, even those that were extended in shape. To pursue these descriptive findings, we injected three electron-dense tracers i.v. and sacrificed the mice 1 h-10 days thereafter. Colloidal carbon, colloidal thorium dioxide (cThO2), and soluble horseradish perixidase (HRP) were actively sequestered into the vacuolar system of macrophages but were interiorized only in trace amounts by FDC\u27s. Therefore, FDC\u27s are not macrophages by cytologic and functional criteria. FDC\u27s did display a unique property. Both colloidal carbon and thorium dioxide, which are nonimmunogens, could be visualized extracellularly on the cell surface for several days. The meaning of this is unclear, but the association of colloid with FDC\u27s appeared to slow the movement of particulates through the extracellular space into the GC proper. FDC\u27s were not readily identified in splenic white pulp lacking GC\u27s. They must develop de novo then, possibly from novel dendritic cells that we have identified in vitro

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