APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa
J. Clin. Invest. Bertrand Huard, et al. 118:2887 doi:10.1172/JCI33760 [Go to this article.]

Figure 2
APRIL-rich niches are formed in subepithelium zone from the tonsillar crypt. (A) Presence of APRIL-producing cells (Stalk-1 staining, 5 μg/ml) in tonsillar crypt epithelium. The arrow indicates a cell stained brightly. (B) Some Stalk-1–stained cells in the epithelium have a trilobular nucleus. (C) These Stalk-1⁺ (green) cells coexpress elastase (red, 1 μg/ml). (D) The crypt epithelium is composed of keratin 8⁺ (1/2, red) cells among other pan-keratin⁺ (1/100, green) and (E) syndecan-1⁺ (10 μg/ml, green) epithelial cells. (F) Keratin 8⁺ (red) and keratin 8^– crypt epithelial cells produce APRIL (Stalk-1; green). Secreted APRIL (red; Aprily-2 staining, 2 μg/ml) is retained on (G) pan-keratin⁺ (green) epithelial cells (H) expressing syndecan-1 (green). The arrow indicates the direction for the crypt lumen. (I) Secreted APRIL (red) accumulates at sites distant from APRIL-producing cells (green) in the subepithelial zone. Original magnification, ×20 (A and I); ×40 (C–H); ×100 (B). Pictures shown are representative of more than 10 crypt epithelia from patients with recurrent tonsillitis. in, tonsillar parenchyma; out, crypt lumen; Pan-Ker, pan-keratin⁺; Ker-8, keratin 8⁺; Syn-1, syndecan-1⁺; Ap-2, Aprily-2.