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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/3741

Title: PRODUCTION AND NUCLEOTIDE-SEQUENCE OF AN INHIBITORY HUMAN-IGM AUTOANTIBODY DIRECTED AGAINST PLATELET GLYCOPROTEIN IA/IIA
Authors: DECKMYN, H
Zhang, JK
VANHOUTTE, E
VERMYLEN, J
Issue Date: 1994
Publisher: W B SAUNDERS CO
Citation: BLOOD, 84(6). p. 1968-1974
Abstract: Human B-cell lines were derived by limiting dilutions of Epstein-Barr virus (EBV) transformed peripheral B cells from a patient with an autoantibody against glycoprotein (GP)Ia/IIa, and manifesting defective collagen-induced platelet aggregation and a bleeding problem. Antibody-producing clones were selected for their reactivity with whole platelets or with affinity-purified GPIa/IIa by enzyme-linked immunosorbent assay (ELISA). One of these cell lines, selected for further evaluation, produced an IgM (E(3)G(6)) that interfered with platelet aggregation responses. Polymerase chain reaction (PCR) amplifications with two different sets of primers specific for human kappa-chains resulted in the rescue of a unique and identical sequence. The same was true for the mu-chain, from which it was concluded that the cell line was monoclonal. Further analysis showed that the kappa variable domain sequence is similar to the germline gene A30, to 2E7, an anti-GPIIb human autoantibody, and to HF2-1/17, a systemic lupus erythematosus (SLE)-associated broad-specificity human autoantibody. Thus, the specificity of our antibody, E(3)G(6) appears to be determined by the mu-chain, the sequence of which is encoded by a V-HIII gene segment strongly homologous to the germline gene DP-77, by a D gene that is not homologous to any of the germline D genes reported to date, and by J(H4) gene segment that is germline. All four mutations versus DP-77 are in CDRs, and result in amino acid substitutions, which implies that E(3)G(6) may have been derived from an antigen-driven response. (C) 1994 by The American Society of Hematology.
Notes: DR H WILLEMS INST,DEPT IMMUNOL,DIEPENBEEK,BELGIUM.DECKMYN, H, CATHOLIC UNIV LEUVEN,CTR MOLEC & VASC BIOL,HERESTR 49,B-3000 LOUVAIN,BELGIUM.
URI: http://hdl.handle.net/1942/3741
ISI #: A1994PG38800033
ISSN: 0006-4971
Type: Journal Contribution
Appears in Collections: Research publications

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