PubMed · 6783317
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M J Potash. 1981. B lymphocyte stimulation.. https://doi.org/10.1016/0092-8674(81)90264-6
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Apoptosis of normal and leukemic immature B-cells in vitro is suppressed when either cell type is grown in direct contact with a feeder layer of bone marrow-derived stromal cells, including fibroblasts, macrophages, endothelial cells, and adipocytes. In this study, our objective was to identify a stromal cell type which is essential for lymphoblast survival and to characterize the molecules involved in lymphoblast adhesion to these cells. In experiments with B-lineage acute lymphoblastic leukemia (ALL) cells (n = 28) and purified CD19(+) cells from normal bone marrow (n = 6) we found that homogeneous populations of bone marrow fibroblasts could sustain survival of normal and leukemic immature B-cells as efficiently as composite bone marrow stromal layers. Electron microscopic studies showed that leukemic lymphoblasts associate with fibroblasts and with the extracellular matrix (ECM) primarily via their specialized cell surface structures. Immunogold labelingsoliduselectron microscopy analysis revealed that the areas of contact between lymphoblasts and fibroblasts contained beta1 integrins (VLA-4 and VLA-5), fibronectin, vascular cell adhesion molecule (VCAM-1), and a cartilage-link protein, CD44. Double immunogold labeling studies disclosed a direct in situ relationship between fibronectin and VLA-4, VLA-5, and CD44. We hypothesize that these molecular interactions either bring lymphoblasts into close physical proximity with other fibroblast-bound or ECM-bound survival factors or provide survival signals themselves.
Spi-B and PU.1 are hematopoietic-specific transcription factors that constitute a subfamily of the Ets family of DNA-binding proteins. Here we show that contrary to previous reports, PU.1 and Spi-B have very different expression patterns. PU.1 is expressed at high levels in B cells, mast cells, megakaryocytes, macrophages, neutrophils, and immature erythroid cells and at lower levels in mature erythrocytes. PU.1 is completely absent from peripheral T cells and most T cell lines based on sensitive RT-PCR assays. In contrast, Spi-B is expressed exclusively in lymphoid cells and can be detected in early fetal thymus and spleen. In situ hybridizations of adult murine tissues demonstrate Spi-B mRNA in the medulla of the thymus, the white pulp of the spleen, and the germinal centers of lymph nodes. Spi-B expression is very abundant in B cells and both Spi-B mRNA and protein are detected in some T cells. In situ hybridization and Northern blot analysis suggest that Spi-B gene expression increases during B cell maturation and decreases during T cell maturation. Gel-retardation experiments show that Spi-B can bind to all putative PU.1 binding sites, but do not reveal any preferred Spi-B binding site. Finally, both PU.1 and Spi-B function as transcriptional activators of the immunoglobulin light-chain enhancer E lambda 2.4 when coexpressed with Pip (PU.1-interaction partner) in NIH-3T3 cells. Taken together, these data suggest that differences in patterns of expression between Spi-B and PU.1 distinguish the function of each protein during development of the immune system.
Activation of telomerase seems to be a prerequisite for immortalization and is found in permanent cell lines and most malignant tumors. Normal somatic cells are generally telomerase negative, except for bone marrow stem cells. Weak activity is also present in peripheral blood cells. In the present study strong telomerase activity was demonstrated in vivo in normal mature cells of the immune system, as well as in malignant lymphomas. Benign lymph nodes had lower telomerase activity than benign tonsils, which exhibited intermediate to high activity comparable with findings in malignant lymphomas. In benign tonsils the activity seemed to be restricted to germinal center B cells. In benign lymphoid tissues telomerase activity correlated with B-cell numbers and cell proliferation, but this was not observed in the lymphoma group. High-grade lymphomas exhibited higher levels of telomerase compared with low-grade cases. The data showed that in vivo activation of telomerase is a characteristic feature of germinal center B cells. Different signals for activation of telomerase are likely to exist, one of them being immune stimulation. The data suggest that telomerase activity in malignant lymphomas can be explained by an "induction and retention" model, ie, transformation occurs in a normal, mature B cell with reactivated telomerase, which is retained in the neoplastic clone.