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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-04-1232.
Submitted April 24, 2002
Accepted July 18, 2002
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
Department of Pathology, University of Iowa College of Medicine, Iowa City, IA, USA
Division of Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN, USA
* Corresponding author; email: thomas-waldschmidt{at}uiowa.edu.
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 allogeneic IUT mice. Results are compared with adult mice give 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 (Ab) 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 transplant results in complete recovery of the B cell compartment, certain elements of the humoral response remain defective.
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