Competition within the early B-cell compartment conditions B-cell reconstitution after hematopoietic stem cell transplantation in nonirradiated recipients

Blood
Allen LiuMarina Cavazzana-Calvo

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 ex...Continue Reading

Citations

May 21, 2009·International Immunology·Nicholas D HuntingtonNuno L Alves
Oct 26, 2006·Proceedings of the National Academy of Sciences of the United States of America·Gustavo MostoslavskyRichard C Mulligan
Nov 17, 2009·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Judith A ShizuruMarina Cavazzana-Calvo
Sep 1, 2006·Expert Review of Clinical Immunology·Marcus Svensson, William W Agace
Feb 22, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kim H T ParaisoWilliam G Kerr
Dec 18, 2020·Frontiers in Immunology·Anna VillaMaria Carmina Castiello
May 11, 2020·The Journal of Allergy and Clinical Immunology·Maria Carmina CastielloLuigi D Notarangelo

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