APRIL production increases in synovium from rheumatoid arthritis patients. (a) Control immunoglobulin (cIg), Stalk-1 and Aprily-2 stainings for a synovium from a rheumatoid arthritis (RA) patient. Arrow: Stalk-1 stained cell present in the lining layer. (b) Two-color immunofluorescence shows that Stalk-1bright cells (green) are elastase+(red) neutrophils. Stalk-1dull cells do not express elastase (arrow). (c) Stalk-1dull cells (green) are macrophages expressing CD68 (red). (d) Stalk-1dull cells produce A proliferation-inducing ligand (APRIL) (green) and are positive for secreted APRIL (red) (arrowhead), while Stalk-1bright cells (arrow) do not. (e) CD68+ macrophages (green) retain secreted APRIL (red). (f) Two-color immunofluorescence and confocal analysis shows that Stalk-1 staining (green) is associated with Aprily-2 (red) staining in a single cell, but is not fully colocalized. Original magnification, 100×. Pictures representative of 11 RA lesions.