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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1232.
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Blood, 15 December 2002, Vol. 100, No. 13, pp. 4557-4564
IMMUNOBIOLOGY
Abnormal T cell-dependent B-cell responses in SCID mice
receiving allogeneic bone marrow in utero
Thomas J. Waldschmidt,
Angela Panoskaltsis-Mortari,
Ronald T. McElmurry,
Lorraine
T. Tygrett,
Patricia A. Taylor, and
Bruce 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.
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.
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