Role of the complement C3 protein in the control of the specific immune response

Whereas complement system was usually considered as a member of innate defence, one of its components (C3) is now thought to facilitate acquired immunity. This role is due first to its capacity to covalently bind to antigens and secondly to the interactions of its proteolytic fragments with different receptors expressed on most cells involved in the acquired immune response. After activation in the plasma, C3 is proteolysed in fragments which possess various biological activities, as a modification in cell activities occurred after binding to cell surface receptors. Injection of low amount of antigen results in a modified immune response in C3 deficient animals with a decrease in the lever of specific antibodies and an absence of IgM/IgG switch. One of the fragments of C3 (C3d) and its receptor (CR2) seem particularly important : knock out animals in C3 or CR2 have similar phenotypes. Mice with a deficit in CR2, restricted to the B lymphocytes present a strong reduction in the number and the size of germinal centers. Moreover, expression of CR2 on follicular dendritic cells is necessary for the generation of a strong memory response. C3 is also involved in the control of the intracellular processing of the antigen as the use of covalent complex (C3b-antigen) instead of free antigen increases the amount of stable MHC class II molecules at the antigen presenting cells surface. In summary. C3 fragments increase cell to cell interactions, induce intracellular signalling after binding to their receptors and increases intracellular processing of antigens. A better knowledge of the different roles of C3 may be useful to modify the immune response and to promote the immune memory, a domain where C3 seems particularly important.