Evidence that the complement system was involved in adaptive immunity can be traced over three decades to the early reports of binding of C3 to circulating lymphocytes and follicular dendritic cells (FDCs) within lymphoid follicles. These findings, combined with experimental results showing that a transient reduction in the amount of circulating complement C3 led to an impairment in antibody response, suggested that the complement system was involved in adaptive immunity.
Complement enhances B cell immunity principally via complement receptors CD21 (which binds iC3b, C3d,g and C3d) and CD35 (which binds the same C3 products as CD21 but also binds C3b and C4b).In mice, the two receptors seem to be coexpressed and represent splice products of a single locus (the Cr2 locus). They are expressed mainly on B cells and FDCs. On B cells, CD21 forms a receptor complex with the signaling protein CD19 and tetraspan protein CD81. Uptake of C3d-coated antigen by cognate B cells results in an enhanced signal via the B cell antigen receptor.Thus, coengagement of the CD21-CD19-CD81 coreceptor with B cell antigen receptor lowers the threshold of B cell activation and provides an important survival signal. A second key mechanism by which complement enhances B cell immunity is by localization of antigen to FDCs within lymphoid follicles. FDCs are specialized stromal cells that secrete the B lymphocyte chemoattractant chemokine and are important in organizing germinal centers within the B cell follicles. FDCs have relatively high expression of CD21 and CD35, and this provides an effective mechanism for retention of C3-coated immune complexes within the lymphoid compartment. How immune complexes are taken up by FDCs is not clear, but an intact classical pathway and CD21 and CD35 receptors are thought to be essential.
1. Carroll M C. (2004). The complement system in regulation of adaptive immunity. Nature immunology, 5(10), 981-986.
2. Hoebe K, et al. (2004). The interface between innate and adaptive immunity. Nature immunology, 5(10), 971-974.