title: Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipients.
abstract: Severe combined immunodeficiency (SCID) is characterized by a complete block in T-lymphocyte differentiation. Most SCID also affects B-cell development or function, although a normal pool of pro-B cells is detectable. Treatment of SCID consists of allogeneic hematopoietic stem cell transplantation (HSCT), but in the absence of a myeloablative conditioning regimen, only T cells, and in some cases, natural killer (NK) cells, are of donor origin, while all other leukocytes subsets are of host origin. We hypothesized that donor B-cell development success could be conditioned by the competitive ability of recipient B-cell precursors in the bone marrow. We therefore compared the outcome of unconditioned HSCT in mice that differed with respect to their pro-B-cell compartments. B-cell reconstitution was limited in recipient mice containing a normal pro-B-cell pool, whereas immature and mature B-cell numbers reached wild-type levels in mice with compromised early B-cell precursors. Interestingly, host NK cells did not modify the outcome of unconditioned HSCT as long as the early B-cell compartment was compromised. These observations suggest that recipient B-cell precursors condition the reconstitution of the donor B-cell pool and, if extrapolative to humans, suggest that conditioning regimens targeting host pro-B cells may help improve B-cell reconstitution after allogeneic HSCT.
authors.affiliation: Développement normal et pathologique du système immunitaire, Institut National de la Santé et de la Recherche Médicale U768-Site Necker-Enfants Malades, Paris Cedex 15, France.
authors.forename: Allen
authors.initials: A
authors.lastname: Liu
authors.forename: Christian A J
authors.initials: CA
authors.lastname: Vosshenrich
authors.forename: Chantal
authors.initials: C
authors.lastname: Lagresle-Peyrou
authors.forename: Michele
authors.initials: M
authors.lastname: Malassis-Seris
authors.forename: Christophe
authors.initials: C
authors.lastname: Hue
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: James P
authors.initials: JP
authors.lastname: Di Santo
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D018183:Transplantation Chimera / Q000276:immunology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous