APCs in the human axillary lymph node associate with the fibroreticular cell network. Frozen lymph node sections were probed with antibodies to either collagen or fibronectin to map the fibroreticular cell network. Multicolor immunohistochemistry illustrated that the majority of CD1a⁺CD207⁻, CD1a⁺CD207⁺ (A,B), and CD208⁺ APCs (C-E) were either in intimate contact with or tethered to fibroreticular cell structures. Most APCs expressing CD209 (F-I) and CD14 (J-L) were also in close contact with fibroreticular cell structures. Interestingly, CD209⁺ and CD14⁺ APCs tended to cluster around ring-like structures resembling high endothelial venules (F-J). Just beneath the outer capsule, there was a narrow void lacking collagen fibers; the CD209⁺ and CD14⁺ APCs distributed along the basement membrane of the capsule were tethered to the collagen fibers at either side of this subcapsular space, possibly sinus (F,G,K,L). Data are representative of 3 independent experiments.