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.

Follicular Dendritic Cell Dedifferentiation by Treatment with an Inhibitor of the Lymphotoxin Pathway Dramatically Reduces Scrapie Susceptibility

“…Antigens are trapped and retained on the surface of FDCs through interactions between complement components and cellular complement receptors (47,50). The loss of expression FIG.…”

A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor

“…The interaction of follicular dendritic cells with activated, antigen-specific B cells serves to rescue them from apoptosis and promote the development of memory B cells. 22 Given its purported cytoprotective role, the secreted clusterin protein may be involved in this process. It is plausible that clusterin may serve a similar role in the interaction between thymic medullary epithelial cells and immature T cells.…”

Production of complement components by cells of the immune system

“…While it is still unclear how many complement proteins are produced by B cells, it is well known that C3-activation products interact via CRs on B cells. Opsonization of an antigen by (i)C3b/ C3d results, via CR2, in stimulation of the B cells, which results subsequently in a lowered threshold to produce antibodies [5,93,94]. Besides the well-studied CR2 and C3d interaction, B cells also express CR1 and CR4 which recognize C3b and its degradation product iC3b [95,96].…”