Extreme leukoreduction of major histocompatibility complex class II positive B cells enhances allogeneic platelet immunity
(1999) In Blood 93(2). p.713-720- Abstract
In a murine model of platelet alloimmunization, we examined the definitive role that mononuclear cells (MC) have in modulating platelet immunity by using platelets from severe combined immunodeficient (SCID) mice. CB.17 (H-2(d)) SCID or BALB/c (H-2(d)) mouse platelets were transfused weekly into fully allogeneic CBA (H-2(k)) mice and antidonor antibodies measured by flow cytometry. MC levels in BALB/c platelets were 1.1 γ 0.6/μL and SCID mouse platelets could be prepared to have significantly lower (<0.05/μL) MC numbers. Transfusions with 108 BALB/c platelets (containing ≃100 MC/transfusion) stimulated IgG antidonor antibodies in 100% of the recipients by the fifth transfusion, whereas 108 SCID mouse platelets... (More)
In a murine model of platelet alloimmunization, we examined the definitive role that mononuclear cells (MC) have in modulating platelet immunity by using platelets from severe combined immunodeficient (SCID) mice. CB.17 (H-2(d)) SCID or BALB/c (H-2(d)) mouse platelets were transfused weekly into fully allogeneic CBA (H-2(k)) mice and antidonor antibodies measured by flow cytometry. MC levels in BALB/c platelets were 1.1 γ 0.6/μL and SCID mouse platelets could be prepared to have significantly lower (<0.05/μL) MC numbers. Transfusions with 108 BALB/c platelets (containing ≃100 MC/transfusion) stimulated IgG antidonor antibodies in 100% of the recipients by the fifth transfusion, whereas 108 SCID mouse platelets (containing ≃5 MC/transfusion) stimulated higher-titered IgG alloantibodies by the second transfusion. When titrations of BALB/c peripheral blood MC were added to the SCID mouse platelets, levels approaching 1 MC/μL reduced SCID platelet immunity to levels similar to BALB/c platelets. Characterization of the alloantibodies showed that the low levels of MC significantly influenced the isotype of the antidonor IgG; the presence of 1 MC/μL was associated with induction of noncomplement fixing IgG1 antidonor antibodies, whereas platelet transfusions, devoid of MC (<0.05/μL), were responsible for complement- fixing IgG2a production. When magnetically sorted defined subpopulations of MC were added to the SCID platelets, major histocompatability complex (MHC) class II positive populations, particularly B cells, were found to be primarily responsible for the reduced SCID mouse platelet immunity. The presence of low numbers of MC within the platelets was also associated with an age-dependent reduction in platelet immunogenicity; this relationship however, was not observed with SCID mouse platelets devoid of MC. The results suggest that a residual number of MHC class II positive B cells within allogeneic platelets are required for maximally reducing alloimmunization.
(Less)
- author
- Semple, John W. LU ; Speck, Edwin R. ; Cosgrave, Donna ; Lazarus, Alan H. ; Blanchette, Victor S. and Freedman, John
- publishing date
- 1999-01-15
- type
- Contribution to journal
- publication status
- published
- in
- Blood
- volume
- 93
- issue
- 2
- pages
- 8 pages
- publisher
- American Society of Hematology
- external identifiers
-
- scopus:0033555792
- pmid:9885234
- ISSN
- 0006-4971
- language
- English
- LU publication?
- no
- id
- f2780473-a469-4a46-bd5c-175677af46f4
- date added to LUP
- 2019-12-03 10:28:42
- date last changed
- 2024-01-16 16:51:07
@article{f2780473-a469-4a46-bd5c-175677af46f4,
abstract = {{<p>In a murine model of platelet alloimmunization, we examined the definitive role that mononuclear cells (MC) have in modulating platelet immunity by using platelets from severe combined immunodeficient (SCID) mice. CB.17 (H-2(d)) SCID or BALB/c (H-2(d)) mouse platelets were transfused weekly into fully allogeneic CBA (H-2(k)) mice and antidonor antibodies measured by flow cytometry. MC levels in BALB/c platelets were 1.1 γ 0.6/μL and SCID mouse platelets could be prepared to have significantly lower (<0.05/μL) MC numbers. Transfusions with 10<sup>8</sup> BALB/c platelets (containing ≃100 MC/transfusion) stimulated IgG antidonor antibodies in 100% of the recipients by the fifth transfusion, whereas 10<sup>8</sup> SCID mouse platelets (containing ≃5 MC/transfusion) stimulated higher-titered IgG alloantibodies by the second transfusion. When titrations of BALB/c peripheral blood MC were added to the SCID mouse platelets, levels approaching 1 MC/μL reduced SCID platelet immunity to levels similar to BALB/c platelets. Characterization of the alloantibodies showed that the low levels of MC significantly influenced the isotype of the antidonor IgG; the presence of 1 MC/μL was associated with induction of noncomplement fixing IgG1 antidonor antibodies, whereas platelet transfusions, devoid of MC (<0.05/μL), were responsible for complement- fixing IgG2a production. When magnetically sorted defined subpopulations of MC were added to the SCID platelets, major histocompatability complex (MHC) class II positive populations, particularly B cells, were found to be primarily responsible for the reduced SCID mouse platelet immunity. The presence of low numbers of MC within the platelets was also associated with an age-dependent reduction in platelet immunogenicity; this relationship however, was not observed with SCID mouse platelets devoid of MC. The results suggest that a residual number of MHC class II positive B cells within allogeneic platelets are required for maximally reducing alloimmunization.</p>}},
author = {{Semple, John W. and Speck, Edwin R. and Cosgrave, Donna and Lazarus, Alan H. and Blanchette, Victor S. and Freedman, John}},
issn = {{0006-4971}},
language = {{eng}},
month = {{01}},
number = {{2}},
pages = {{713--720}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Extreme leukoreduction of major histocompatibility complex class II positive B cells enhances allogeneic platelet immunity}},
volume = {{93}},
year = {{1999}},
}