International Immunology, Vol 9, 913-921, Copyright © 1997 by Oxford University Press
J George, M Blank, B Gilburd, M Hojnik, B Shenkman, I Tamarin, D Varon, E Matsuura, T Koike and Y Shoenfeld
beta 2-Glycoprotein I (beta 2GPI) is a 50 kDa molecule proposed as a
principal target of 'autoimmune' antiphospholipid antibodies (aPL). We have
used deleted mutants (DM) representing different domains of beta 2GPI
(I-IV, IV-V and V) for immunization of naive mice and studied the
characteristics of the respective murine IgG preparations in comparison
with affinity-purified IgG from two patients with primary antiphospholipid
syndrome. Immunization with beta 2GPI and with the DM produced anti-beta
2GPI antibodies, part of which reacted with negatively charged
phospholipids (PL), whereas reactivity with cardiolipin was evident only in
the IgG from mice immunized with beta 2GPI. These results are consistent
with the presumption that aPL are induced following the in vivo association
of beta 2GPI (used for immunization) with resident negatively charged PL.
Accordingly, DM which either lack the PL binding site or aPL attachment
locus did not elicit, upon immunization, antibodies reactive with PL.
Further, murine anti-beta 2GPI IgG and human 'autoimmune' aPL were similar,
albeit not identical, in terms of DM requirement for PL binding and charge
dependency. Murine antibodies and human aPL, regardless of their binding
characteristics, were found to bind significantly to platelets upon their
activation with thrombin and to promote platelet activation. The results of
the current study emphasize the dissimilarities between human 'autoimmune'
aPL and murine anti-beta 2GPI. Thus, anti-beta 2GPI antibodies to different
DM as well as human aPL are capable of binding and activating human
platelets provided beta 2GPI is present.
ARTICLES
Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human beta 2-glycoprotein I
Department of Medicine B, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
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