Cell and Molecular Biology of Human Complement Receptors

Abstract

Complement receptors type 1 (CR1) and type 2 (CR2) mediate the uptake by various cell types of complexes bearing the covalently bound fragments of C3: C3b and iC3b are ligands for CR1, and iC3b and C3dg are the ligands for CR2. CR1 is expressed by several types of leukocytes, erythrocytes, and glomerular podocytes, whereas CR2 is found on B lymphocytes and follicular dendritic cells. CR1 is involved in clearance of microbial pathogens and immune complexes, and CR2 has a role in the regulation of B lymphocyte function. Despite the differing functions of CR1 and CR2, these two receptors share certain structural characteristics: they have homologous amino acid and nucleotide sequences; they have similar overall organizations, being comprised of repeating units of 60–70 amino acids that are present in other C4b/C3b-binding proteins; and their genes localize to the same region of chromosome 1. In addition, the functions of both CR1 and CR2 may be regulated by phosphorylation. It is proposed that CR2 evolved from CR1 to provide the B cell with a capacity for stimulation by complexes bearing iC3b and C3dg because this cell type, in contrast to myelomonocytic cells, is usually distant from the site of complement activation.