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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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-03109725
Contributor : Christian Vosshenrich <>
Submitted on : Wednesday, January 13, 2021 - 10:49:41 PM
Last modification on : Thursday, May 27, 2021 - 5:08:05 PM

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Allen Liu, Christian A. J. Vosshenrich, Chantal Lagresle-Peyrou, Michele Malassis-Seris, Christophe Hue, et al.. Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipients. Blood, American Society of Hematology, 2006, 108 (4), pp.1123-1128. ⟨10.1182/blood-2006-01-0061⟩. ⟨pasteur-03109725⟩

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