Long-term chimerism and B-cell function after bone marrow transplantation in patients with severe combined immunodeficiency with B cells: A single-center study of 22 patients.

Abstract

We retrospectively analyzed the B-cell function and leukocyte chimerism of 22 patients with severe combined immunodeficiency with B cells (B(+) SCID) who survived more than 2 years after bone marrow transplantation (BMT) to determine the possible consequences of BMT procedures, leukocyte chimerism, and SCID molecular deficit on B-cell function outcome. Circulating T cells were of donor origin in all patients. In recipients of HLA-identical BMT (n = 5), monocytes were of host origin in 5 and B cells were of host origin in 4 and of mixed origin in 1. In recipients of HLA haploidentical T-cell-depleted BMT (n = 17), B cells and monocytes were of host origin in 14 and of donor origin in 3. Engraftment of B cells was found to be associated with normal B-cell function. In contrast, 10 of 18 patients with host B cells still require Ig substitution. Conditioning regimen (ie, 8 mg/kg busulfan and 200 mg/kg cyclophosphamide) was shown neither to promote B-cell and monocyte engraftment nor to affect B-cell function. Eight patients with B cells of host origin had normal B-cell function. Evidence for functional host B cells was further provided in 3 informative cases by Ig allotype determination and by the detection, in 5 studied cases, of host CD27(+) memory B cells as in age-matched controls. These results strongly suggest that, in some transplanted patients, host B cells can cooperate with donor T cells to fully mature in Ig-producing cells.

• Authors: E Haddad, F Le Deist, P Aucouturier, M Cavazzana-Calvo, S Blanche, G De Saint Basile, A Fischer
• Journal: Blood (Blood) Vol. 94 Issue 8 Pg. 2923-30 (Oct 15 1999) ISSN: 0006-4971 [Print] United States
• PMID: 10515898 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Interleukin-2
• Cyclophosphamide
• Protein-Tyrosine Kinases
• JAK3 protein, human
• Janus Kinase 3
• Busulfan

Topics

• Antibody Formation
• B-Lymphocytes (immunology)
• Bone Marrow Transplantation (immunology)
• Busulfan
• Chimera
• Cyclophosphamide
• Graft Survival
• Hematopoiesis
• Humans
• Immunocompromised Host
• Immunologic Memory
• Infant
• Janus Kinase 3
• Lymphocyte Cooperation
• Monocytes
• Protein-Tyrosine Kinases (deficiency, genetics)
• Receptors, Interleukin-2 (deficiency, genetics)
• Retrospective Studies
• Severe Combined Immunodeficiency (classification, genetics, therapy)
• T-Lymphocytes
• Transplantation Conditioning