Bone marrow stroma-dependent modulation of CD45R isoform expression on Abelson virus transformed pre-B cells.
The CD45 glycoprotein family exhibits cell-lineage-associated structural heterogeneity which is due, in part, to alternative pre-mRNA splicing. The Abelson murine leukemia (A-MuLV) preferentially transforms immature B cells that express a B-cell-specific high molecular weight CD45 isoform, called B220. However, we observed that A-MuLV-transformed cell lines are often B220- while maintaining high levels of "pan" CD45 expression. In vitro transformation of murine bone marrow revealed that the stromal microenvironment over which A-MuLV-transformed lymphoblasts are grown affected the B220 phenotype of the pre-B cells. Over a period of a few weeks, B220+ populations grown over a clonal stromal cell line gradually became B220-. However, the transition from a B220+ to B220- phenotype was dependent on the lot of fetal calf serum used. In contrast, cells grown over a heterogeneous bone marrow stroma maintained B220+ expression for long periods of time. The appearance of B220- cells in clonal B220+ populations indicated that the change in phenotype resulted in part from modulation of B220 expression. B220- B-cell lines did not express the high molecular weight CD45 RNA species indicating that the B220- phenotype was due to alternative pre-mRNA splicing. Finally, the shift from B220+ to B220- was not accompanied by changes in the stage of development of the cultures. These observations demonstrate that expression of B220 is not required for the continued proliferation of Abelson-transformed pre-B cells and is regulated by unknown environmental factors.
Fizzotti
M
M
Department of Human Oncology, University of Wisconsin Medical School, Madison 53792, USA.
Clark
S S
SS
D000011:Abelson murine leukemia virus / Q000502:physiology; D000818:Animals; D016525:Antigenic Modulation / Q000276:immunology*; D000954:Antigens, Surface / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology*; D015139:Blotting, Southern; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000276:immunology; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D007536:Isomerism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis* / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D017154:Stromal Cells / Q000166:cytology
D000954:Antigens, Surface; D017493:Leukocyte Common Antigens