Reduced expression of vascular cell adhesion molecule-1 on bone marrow stromal cells isolated from marrow transplant recipients correlates with a reduced capacity to support human B lymphopoiesis in vitro.
A common sequela to allogeneic or autologous bone marrow transplantation (BMT) is a delay in the reconstitution of a functional B-cell immune response. Therefore, we examined whether the posttransplant BM microenvironment is deficient in supporting the proliferation and/or differentiation of B-cell precursors. BM stromal cell cultures were established from patients who received allogeneic or autologous BMT for acute lymphoblastic leukemia, Hodgkin's disease, or non-Hodgkin's lymphoma. These cultures were then compared with normal donor BM stromal cell cultures for expression of adhesion molecules and the capacity to support the adhesion and interleukin-7 (IL-7)-dependent growth of normal B-cell precursors. Analysis of BM stromal cell cultures established from 28 BMT recipients showed a significantly reduced expression of cell surface vascular cell adhesion molecule-1 (VCAM-1/CD106), compared with normal donor BM stromal cells. Transplant BM stromal cell CD106 expression was responsive to regulatory cytokines in a manner qualitatively comparable with normal donor BM stromal cells. The level of B-cell precursor adhesion to transplant BM stromal cells correlated with the level of CD106 expression. Of 19 evaluable transplant BM stromal cell cultures, eight exhibited a reduced capacity to support the growth of CD19+/light chain- normal B-cell precursors. The capacity of transplant BM stromal cells to support B-cell precursor growth correlated with the level of CD106 expression, and the level of B-cell precursor adhesion. Our collective results may provide new mechanistic insight into why B-cell recovery is delayed post-BMT and underscore the importance of VCAM-1/CD106 in regulating B lymphopoiesis.
Dittel
B N
BN
Department of Laboratory Medicine/Pathology, University of Minnesota Medical School, Minneapolis 55455, USA.
LeBien
T W
TW
D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D005434:Flow Cytometry; D006410:Hematopoiesis / Q000502:physiology*; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy; D017154:Stromal Cells / Q000737:chemistry* / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D015851:Interleukin-7; D019010:Vascular Cell Adhesion Molecule-1; D015847:Interleukin-4