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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1123-1128.
Prepublished online as a Blood First Edition Paper on April 13, 2006; DOI 10.1182/blood-2006-01-0061.
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Submitted January 6, 2006
Accepted March 31, 2006
Competition within the early B cell compartment conditions B cell reconstitution after hematopoietic stem cell transplantation in non-irradiated recipients
Allen Liu, Christian A Vosshenrich, Chantal Lagresle-Peyrou, Michele Malassis-Seris, Christophe Hue, Alain Fischer, James P Di Santo, and Marina Cavazzana-Calvo*
Developpement normal et pathologique du systeme immunitaire, Inserm U768, Site Necker-Enfants Malades; Faculte de Medecine Universite Rene Descartes Paris V, Paris, France
Unite des Cytokines et Developpement Lymphoide, Inserm U668, Institut Pasteur, Paris, France
Developpement normal et pathologique du systeme immunitaire, Inserm U768, Site Necker-Enfants Malades; Faculte de Medecine Universite Rene Descartes Paris V, Paris, France; Biotherapy Department, AP-HP, Hopital Necker-Enfants Malades, Paris, France
Developpement normal et pathologique du systeme immunitaire, Inserm U768, Site Necker-Enfants Malades; Faculte de Medecine Universite Rene Descartes Paris V, Paris, France; Unite d'Immuno-Hematologie Pediatrique, Departement de Pediatrie, Hopital Necker-Enfants Malades, Paris, France
* Corresponding author; email: m.cavazzana{at}nck.ap-hop-paris.fr.
Severe Combined Immunodeficiency (SCID) is characterized by a complete block in T-lymphocyte differentiation. Most SCID also affect 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 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.
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