Abstract
β2-Glycoprotein I (β2GPI) 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 β2GPI (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 β2GPI and with the DM produced anti-β2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with β2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of β2GPI (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-β2GPI 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-β2GPI. Thus, anti-β2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided β2GPI is present.
| Original language | English |
|---|---|
| Pages (from-to) | 913-921 |
| Number of pages | 9 |
| Journal | International Immunology |
| Volume | 9 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1997 |
| Externally published | Yes |
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Keywords
- β-glycoprotein I
- Antibodies
- Antiphospholipid syndrome
- Autoimmunity
- Platelets
ASJC Scopus subject areas
- Immunology
Cite this
Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human β2-glycoprotein I. / George, Jacob; Blank, Miri; Gilburd, Boris; Hojnik, Maya; Shenkman, Boris; Tamarin, Iiia; Varon, David; Matsuura, Eiji; Koike, Takao; Shoenfeld, Yehuda.
In: International Immunology, Vol. 9, No. 6, 1997, p. 913-921.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human β2-glycoprotein I
AU - George, Jacob
AU - Blank, Miri
AU - Gilburd, Boris
AU - Hojnik, Maya
AU - Shenkman, Boris
AU - Tamarin, Iiia
AU - Varon, David
AU - Matsuura, Eiji
AU - Koike, Takao
AU - Shoenfeld, Yehuda
PY - 1997
Y1 - 1997
N2 - β2-Glycoprotein I (β2GPI) 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 β2GPI (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 β2GPI and with the DM produced anti-β2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with β2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of β2GPI (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-β2GPI 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-β2GPI. Thus, anti-β2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided β2GPI is present.
AB - β2-Glycoprotein I (β2GPI) 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 β2GPI (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 β2GPI and with the DM produced anti-β2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with β2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of β2GPI (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-β2GPI 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-β2GPI. Thus, anti-β2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided β2GPI is present.
KW - β-glycoprotein I
KW - Antibodies
KW - Antiphospholipid syndrome
KW - Autoimmunity
KW - Platelets
UR - http://www.scopus.com/inward/record.url?scp=8244226657&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8244226657&partnerID=8YFLogxK
U2 - 10.1093/intimm/9.6.913
DO - 10.1093/intimm/9.6.913
M3 - Article
C2 - 9199975
AN - SCOPUS:8244226657
VL - 9
SP - 913
EP - 921
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 6
ER -