Studies of the Human Lymphocyte Receptor for Heat-Aggregated or Antigen-Complexed Immunoglobulin

Abstract

A mouse lymphocyte receptor for antibody complexed to antigen has been described by several laboratories (1-5). The receptor appeared to be characteristic of bone marrow-(or nonthymus)-derived (B) lymphocytes; binding to the receptor was apparently complement independent; the receptor formed a stable bond to antibody only when the latter was complexed to antigen; binding to the receptor was not inhibited by antimouse immunoglobulin; and the receptor appeared to have binding specificity for the Fc portion of the antibody molecule.In what appears to be an analogous observation, a human lymphocyte receptor for heat-aggregated immunoglobulin (Ig) complexes has been described (6-9). In normal human peripheral blood, the receptor was found on both B cells and a small subpopulation of lymphocytes (mean 3.6%) which bore both thymus-derived (T) and B-cell markers. In certain cases of chronic lymphocytic leukemia or hypogammaglobulinemia, the receptor was detected on some peripheral blood lymphocytes (PBL) ~ which appeared to be B cells but which lacked easily detectable surface Ig. The binding of aggregated Ig to this receptor was not dependent on complement, divalent cations, or temperature, and was not inhibited by polyvalent (% #, K, X) anti-Ig.The present studies were carried out to further characterize the human lymphocyte receptor for complexed Ig. Data from these studies indicate that: (a) the receptor has specificity for the Fc portion of complexed Ig, and it appears that the site on the Fc is dependent on disulfide bond(s); (b) heat-aggregated Ig and antigen-complexed Ig bind to the same receptor; (c) the receptor for complexed antibody is distinct from surface Ig and appears to be a trypsinresistant protein or glycoprotein; (d) membrane-bound Ig complexes do not readily accumulate at one pole of the cell (cap formation) unless they are subsequently cross-linked with anti-Ig; (e) the receptor is necessary for antibody-* A portion of this work was supported by contract no. NIH-N01-CB-02207. 1 Abbreviations used in this paper: BSA-PBS, 2% bovine serum albumin in phosphatebuffered saline, pH 7.2 or 8.0 with or without Na Azide 0.02%; FCS, fetal calf serum; FITC, fluorescein isothiocyanate; f/p, absorption ratio (495 nm or 515 nm/280 rim); HSA human serum albumin; KLH, keyhole limpet hemocyanin; PBS, phosphate-buffered saline, pH 7.2 or 8.0, 0.05 M PO4 and 0.15 M NaC1; TMRITC, tetramethylrhodamine isothiocyanate. 5 0 8

EVIDENCE FOR IDENTITY OR CLOSE ASSOCIATION OF THE Fc RECEPTOR OF B LYMPHOCYTES AND ALLOANTIGENS DETERMINED BY THE Ir REGION OF THE H-2 COMPLEX

“…(Received for publication 10 June 1974) Studies in several species, including mouse and man, have shown that B lymphocyteS bear on their surface membranes a receptor (termed the Fc receptor) which specifically binds heat-aggregated or antigen-complexed immunoglobulin (complexed Ig l) (1)(2)(3)(4)(5)(6). The receptor is distinct from lymphocyte surface Ig (2-4) and the C3 receptor (6), and appears to be a trypsin-resistant protein or glycoprotein (4).…”

Receptors for human immunoglobulin on acute myeloid leukaemic leucocytes

“…This irregular and patchy staining is similar to that seen when aggregated IgG bound to lymphocyte Fc receptors is stained with an anti-immunoglobulin fluorescent conjugate (Dickler Fe RECEPTORS ON AML LEUCOCYTES and Kunkel, 1972;Dickler, 1974 that these receptors can be further unmasked or blocked respectively, suggesting that at least part of the AML surface Ig is bound in vivo to Fc receptors. The results in this paper also show that the relatively rapid rosette test described could be useful in the diagnosis of AMML using peripheral blood leucocytes, as an adjunct to conventional bone marrow diagnosis.…”

“…That the receptor recognizes the Fc fragment of IgG has been demonstrated by the inhibition of IgG binding to cells by isolated Fc but not Fab or F(ab')2 fragments (Abramson et al, 1970b;Messner and Jelinek, 1970;Fr0land et al, 1974a). Although Fc receptors are important for the phagocytosis of antigen-antibody complexes by monocytes and macrophages, Fudenberg, 1968, Huber, Douglas andFudenberg, 1969) and in antibody-dependent lymphocyte-mediated cytotoxicity (Dickler, 1974;Wisl0ff, Fr0land and Michaelson, 1974) the functional significance of Fc receptors in vivo still remains unclear. Nevertheless, Fc receptors are to be found on many cell types, both phagocytic and non-phagocytic, involved in the immune response.…”

Immunoglobulins associated with human tumours in vivo: igg concentrations in eluates of colonic carcinomas

“…That a substantial proportion of tumour-associated Ig is associated with Fc receptors is suggested by the observation of an inverse relationship between the amount of IgG on human tumours and their Fc receptor activity, and prolonged washing of the tumours decreased surface Ig and increased Fcreceptor activity (Tonder et al, 1976). Fc receptors have much higher affinity for antigen-antibody complexes or aggregated Ig than for native Ig (Dickler, 1974). Such complexes could form when there is antigen shedding from the tumour, which may be associated with tumour progression (Currie & Alexander, 1974).…”