Journal article
Abnormal T cell–dependent B-cell responses in SCID mice receiving allogeneic bone marrow in utero
Blood, Vol.100(13), pp.4557-4564
12/15/2002
DOI: 10.1182/blood-2002-04-1232
PMID: 12393436
Abstract
In allogeneic hematopoietic stem cell transplant recipients, restoration of humoral immunity is delayed and can remain impaired for years. In many severe combined immune deficiency (SCID) patients given haploidentical bone marrow (BM), lesions in humoral immunity are exacerbated by poor engraftment of donor B cells. The nature of these defects is important to understand as they render patients susceptible to infection. Previous work in mice suggested that in utero transplantation (IUT) of allogeneic BM might offer several advantages for the correction of primary immune deficiencies. In SCID mice given fully allogeneic BM in utero, the lymphoid compartment was restored with minimal evidence of graft-versus-host disease (GVHD). The present report examines B-cell reconstitution and function in mice that have received allogeneic IUT. Results are compared with those of adult mice given total body irradiation (TBI) followed by transplantation with allogeneic BM. In addition to enumerating the various B-cell subsets present in BM, spleen, and peritoneal cavity (PC), B-cell competence was assessed by challenging mice with T cell–independent (TI) and T cell–dependent (TD) antigens. The results demonstrated that all B-cell subsets in the BM and periphery were restored in allogeneic IUT and TBI mice, as were antibody responses after TI challenge. Upon immunization with TD antigens, however, IUT and TBI mice exhibited suboptimal responses as measured by the capacity to isotype switch and generate germinal center (GC) B cells. Thus, although allogeneic BM transplantation results in complete recovery of the B-cell compartment, certain elements of the humoral response remain defective.
Details
- Title: Subtitle
- Abnormal T cell–dependent B-cell responses in SCID mice receiving allogeneic bone marrow in utero
- Creators
- Thomas J Waldschmidt - From the Department of Pathology, University of Iowa College of Medicine, Iowa City, and the Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, MinneapolisAngela Panoskaltsis-Mortari - From the Department of Pathology, University of Iowa College of Medicine, Iowa City, and the Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, MinneapolisRonald T McElmurry - From the Department of Pathology, University of Iowa College of Medicine, Iowa City, and the Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, MinneapolisLorraine T Tygrett - From the Department of Pathology, University of Iowa College of Medicine, Iowa City, and the Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, MinneapolisPatricia A Taylor - From the Department of Pathology, University of Iowa College of Medicine, Iowa City, and the Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, MinneapolisBruce R Blazar - From the Department of Pathology, University of Iowa College of Medicine, Iowa City, and the Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.100(13), pp.4557-4564
- DOI
- 10.1182/blood-2002-04-1232
- PMID
- 12393436
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 12/15/2002
- Academic Unit
- Pathology
- Record Identifier
- 9984046912602771
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