The covalent interaction of C3 with IgG immune complexes

Antigens (Ags) are converted into immune complexes (antigen-antibody comple xes, IC) as soon as they encounter their specific antibodies (Abs). In flui ds containing complement, the process of IC formation and fixation of compl ement components occur simultaneously. Hence, the formation of Ag-Ab-comple ment complexes is the normal way of eliminating Ags from a host. C3b-C3b-Ig G covalent complexes are immediately formed on interaction of serum C3 with IgG-IC. These C3b-C3b dimers constitute the core for the assembly of C3/C5 -convertase on the IC, which are subsequently converted into iC3b-iC3b-IgG by the complement regulators. These complexes are detected on SDS-PAGE by t wo bands of molecular composition, C3 alpha 65-C3 alpha 43 (band A) and C3 alpha 65-heavy chain of the Ab (band B), which correspond to C3b-C3b and C3 b-IgG covalent interaction respectively, and that identify opsonized IC (C3 b-IC). C3b can attach to Fab and Fc regions of the Kb molecule with similar efficiency. The presence of multiple C3b binding regions on IgG is conside red an advantageous characteristic that facilitates the elimination of Ags in the form of C3b(n)-IC. Ab molecules on the IC recognize the Ag, and also serve as a very good acceptor for C3b binding. In this way, Ags, even if t hey have no acceptor sites for C3b, can be efficiently processed and remove d. When C3 is activated in serum by IC or other activators, secondary C3b-I gG covalent complexes are generated, with bystander monomeric circulating I gG, and thus constitute, physiological products of complement activation. T hese complexes gain importance when IgG concentration is extremely high as in cases of infusion of intravenous IgG (IVIG) in several pathologies. The covalent attachment of activated complement C3 (C3b, iC3b, C3 d,g) to Ags o r IC links innate and adaptative immunity by targeting Ags to different cel ls of the immune system (follicular dendritic cells, phagocytes, B cells). Hence C3b marks Ags definitively, from the earliest contact with the innate immune system until their complete elimination from the host. (C) 1999 Els evier Science Ltd. All rights reserved.