IDENTIFICATION OF THE MEMBRANE RECEPTOR FOR THE COMPLEMENT FRAGMENT C3d BY MEANS OF A MONOCLONAL

Several cleavage products of complement component C3 interact with cellular membrane receptors and are associated with important biological activities . The larger fragment of activated C3 (C3b), which binds covalently to surface membranes or antigen-antibody complexes, is a ligand for complement receptor type I (CRI),' a glycoprotein of ^-200,000 Mr found on erythrocytes, phagocytes, lymphocytes and other cells (reviewed in reference 1) . CRI has the unusual property of serving as a cofactor for the further fragmentation of bound C3b by a serum enzyme, C3b-inactivator (I) (2-4). The serum factor 011-1 (H) can also serve as a cofactor for the reaction between I and covalently bound C3b, but it is much less effective than CR I on a molar basis (5) . The initial cleavage reaction of C3b releases a peptide of 3,000 M, from its a' chain (6). The remaining fragment (iC3b) has greatest binding affinity for membrane receptor CR3 (7), which is found on phagocytes and natural killer cells . It has been suggested that CR3 consists of two polypeptides of 185,000 and 95,000 M, (8, 9) . Additional cleavages of iC3b by CRI plus I generate C3c (140,000 M,), which is released into the fluid phase, and C3dg (41,000 M,) (24, 10) . The bound C3dg fragment can be further cleaved in vitro by plasmin, elastase, and other proteases, into a fragment called C3d (^35,000 M,) (10) . Indicator particles bearing C3d can attach to and form rosettes with a subpopulation of B lymphocytes (11, 12) and with monocytes after their cultivation on glass surfaces (13) . The membrane molecules that mediate this interaction are operationally defined as CR2. Some studies indicate that, in addition to C3d, CR2 also binds iC3b and C3dg, but the relative affinities of these multiple ligands for the receptor have not been measured (7) . The purpose of this paper is to present evidence that CR2 is a glycoprotein of 140,000 M, called B2 that had