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

Blood. 1999 Oct 15;94(8):2923-30.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Formation
  • B-Lymphocytes / immunology*
  • Bone Marrow Transplantation / immunology*
  • Busulfan
  • Chimera*
  • Cyclophosphamide
  • Graft Survival*
  • Hematopoiesis
  • Humans
  • Immunocompromised Host
  • Immunologic Memory
  • Infant
  • Janus Kinase 3
  • Lymphocyte Cooperation*
  • Monocytes
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics
  • Receptors, Interleukin-2 / deficiency
  • Receptors, Interleukin-2 / genetics
  • Retrospective Studies
  • Severe Combined Immunodeficiency / classification
  • Severe Combined Immunodeficiency / genetics
  • Severe Combined Immunodeficiency / therapy*
  • T-Lymphocytes
  • Transplantation Conditioning

Substances

  • Receptors, Interleukin-2
  • Cyclophosphamide
  • Protein-Tyrosine Kinases
  • JAK3 protein, human
  • Janus Kinase 3
  • Busulfan