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

• Published in: Blood 1995-10, Vol.86 (7), p.2833-2841
• Main Authors: DITTEL, B. N, LEBIEN, T. W
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; B-Lymphocytes - cytology; Biological and medical sciences; Bone Marrow Cells; Bone Marrow Transplantation; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Adhesion; Cell Adhesion Molecules - analysis; Cell Differentiation; Cell Division; Cells, Cultured; Flow Cytometry; Hematopoiesis - physiology; Hodgkin Disease - therapy; Humans; Interleukin-1 - pharmacology; Interleukin-4 - pharmacology; Interleukin-7 - pharmacology; Lymphoma, Non-Hodgkin - therapy; Medical sciences; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Stromal Cells - chemistry; Stromal Cells - physiology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Vascular Cell Adhesion Molecule-1
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V86.7.2833.2833

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.