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Production and nucleotide sequence of an inhibitory human IgM autoantibody
directed against platelet glycoprotein Ia/IIa
H Deckmyn, J Zhang, E Van Houtte and J Vermylen
Center for Molecular and Vascular Biology, University of Leuven, Belgium.
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
(E3G6) 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, E3G6, appears to be determined by the
mu-chain, the sequence of which is encoded by a VHIII 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 JH4 gene segment
that is germline. All four mutations versus DP- 77 are in CDRs, and result
in amino acid substitutions, which implies that E3G6 may have been derived
from an antigen-driven response.
Volume 84,
Issue 6,
pp. 1968-1974,
09/15/1994
Copyright © 1994 by The American Society of Hematology
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