Disturbed secondary structure of lymph nodes in ICOS deficiency. Formalin-embedded inguinal lymph nodes of patient no. 1 and a control patient with carcinoma of the vulva were stained for B cells (CD20), T cells (CD3), and the CD4⁺ and CD8⁺ subsets, respectively (A). The ICOS-deficient lymph node contained fewer and smaller B-cell follicles, which were surrounded mainly by CD8⁺ T cells. The few germinal centers (MIB-1⁺, bcl-6⁺) appeared rudimentary (B). In one lymph node of the ICOS-deficient patient, several granulomata (*) with giant cells (arrow) were present, disrupting the follicular structure (C).