The role of complement in the acquired immune response

Abstract

Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation to specific T cells; the activation of a CD21/CD19 complex-mediated signalling pathway in B cells, which provides a stimulus synergistic to that induced by antigen interaction with the B-cell receptor (BCR); and promotion of the interaction between B cells and FDC, where C3d-bearing immune complexes participate in intercellular bridging. Finally, current studies suggest that CR2 may also play a role in the determination of B-cell tolerance towards self-antigens and thereby hold the key to the previously observed correlation between deficiencies of the early complement components and autoimmune disease.

Figure 1

Signalling processes induced by ligation of B-cell receptor (BCR), complement receptor type 2 (CR2) and FcγRII with opsonized antigen and immune complexes. Ag, antigen; IC, immune complexes; IgG, immunoglobulin G; IgM, immunoglobulin M; ITAM, immunoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-based inhibition motif; Ops. opsonized; PI-3K, phosphatidylinositol-3 kinase; PTK, protein tyrosine kinase; SHIP, inositol phosphate 5-phosphatase; SHP-2, protein tyrosine phosphatase, SHP-2; Vav, guanidine nucleotide exchange factor, Vav. ↑, activation; ↓, inhibition; –, no effect; *, for Ag-specific or non-specific B cells, respectively.