Complement activation inhumanlymphoid germinal centres

SUMMARY Thepresenceofcomplement activation products hasbeenstudied inmorphologically normalhuman lymphatic tissue fromtonsil, spleen andlymphnode.Newlyestablished monoclonal antibodies (mAbs)withreactivity against theC4cleavage fragments C4a,C4b,C4candC4dwere applied on cyrostat sections intheindirect immunoperoxidase staining technique. Irrespective oforgan type, C4dactivation product could bedetected ingerminal centres ofall secondary lymphoid follicles. To substantiate this finding, thecomplete sequenceofcomplement activation products was investigated byaseries ofmono- andpolyclonal antibodies tothecomplement proteins C1,C2,C3,factor B,C5, C9toC5b-9neoantigens andtotheregulatory complement proteins C4binding protein (C4bp), factor I,factor H andproperdin. Similar toC4d,allsecondary follicles exhibited a strongstaining reaction forC3dantigens restricted togerminal centres. Atthe same site, albeit withdistinctly weaker intensity, components ofthemembrane attack complex (MAC)C5b-9 werefound. Thesimultaneous deposition ofCl,C4bandC4bpincertain germinal centres indicates that complement activation is induced viatheclassical pathway. Concomitant deposition ofIgMsuggests IgM-antigen complexes thathavebeentrapped on follicular dendritic cells (FDC)during normal immuneresponseasthe mostlikely candidates foractivators oftheclassical pathway. Ourdatademonstrate thathuman lymphoid germinal centres as important sites ofimmuneregulation closely interrelate withthe complete cascade ofcomplement-activation products, including themembraneattack complex (MAC).