title: 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.affiliation: Unité d'Immunologie et d'Hématologie Pédiatriques, Laboratoire d'Immunologie Clinique, INSERM U25, Hôpital Necker-Enfants Malades, Paris, France. ehaddad@igr.fr
authors.forename: E
authors.initials: E
authors.lastname: Haddad
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: P
authors.initials: P
authors.lastname: Aucouturier
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: S
authors.initials: S
authors.lastname: Blanche
authors.forename: G
authors.initials: G
authors.lastname: De Saint Basile
authors.forename: A
authors.initials: A
authors.lastname: Fischer
mesh_terms: D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002066:Busulfan; D002678:Chimera; D003520:Cyclophosphamide; D006085:Graft Survival; D006410:Hematopoiesis; D006801:Humans; D016867:Immunocompromised Host; D007156:Immunologic Memory; D007223:Infant; D053616:Janus Kinase 3; D008211:Lymphocyte Cooperation; D009000:Monocytes; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000145:classification / Q000235:genetics / Q000628:therapy*; D013601:T-Lymphocytes; D019172:Transplantation Conditioning
chemical_list: D015375:Receptors, Interleukin-2; D003520:Cyclophosphamide; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3; D002066:Busulfan