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Advances in Hematology
Volume 2014 (2014), Article ID 470242, 7 pages
Research Article

RhD Specific Antibodies Are Not Detectable in HLA-DRB1 Mice Challenged with Human RhD Positive Erythrocytes

1The Canadian Blood Services, Canada
2Department of Laboratory Medicine and the Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, 30 Bond Street, Toronto, ON, Canada M5B 1W8
3Immunohematology Reference Laboratory, BloodCenter of Wisconsin, Milwaukee, WI 53226, USA
4Department of Transfusion Medicine, St. Michael’s Hospital, Toronto, ON, Canada M5B 1W8
5Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON, Canada

Received 7 November 2014; Revised 15 December 2014; Accepted 16 December 2014; Published 31 December 2014

Academic Editor: Thomas Kickler

Copyright © 2014 Lidice Bernardo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB1 to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB1 as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW), CD1(ICR), and NSA(CF-1). DRB1 mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB1 mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB1 mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB1 transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed.