Altered CD45 expression in malignant B-1 cells.
CD45 is an important surface glycoprotein which has an intrinsic tyrosine phosphatase activity and has been implicated in cell proliferation, signaling, and differentiation and is associated with the B cell receptor during signaling. In this manuscript, the role of CD45 expression in the development of B-1 malignancies in NZB mice, which serve as a model for human diseases such as chronic lymphocytic leukemia, was investigated. B-1 cells spontaneously hyperproliferate and form a clonal hyperdiploid malignant population in aging NZB mice. Phenotypic analysis indicates that the NZB malignant B-1 cells are bright for IgM, but have reduced levels of CD45 relative to normal, nonmalignant B cells (both B-1 and B-2) and are characterized by dull or negative expression of the CD45 isoform B220/6B2 normally found on all B cells. Malignant B-1 cells demonstrated decreased RNA levels of CD45 relative to IgM expression, while nonmalignant B-2 cells showed similar levels of RNA expression for both CD45 and IgM. As CD45 exists in several isoforms and B cells express the highest molecular weight isoform (B220), malignant B-1 cells were further analyzed with respect to their isoform usage. Although, at the RNA level malignant B-1 cells showed the presence of the of the B220 form of CD45, western blot analysis of B220 protein suggested a posttranslational glycosylation defect in the CD45/B220 expression recognized by the mAb 6B2. F1 recipients of premalignant NZB B-1 cells which had been sorted for IgMhi, B220/6B2negative cells developed hyperdiploid malignant donor B-1 clones earlier than did recipients of NZB B-1 cells which were bright for B220/6B2. However, all the malignant B-1 clones of NZB origin which developed in recipients of both transfer populations were B220/6B2 negative. This indicated that abnormal expression of CD45 may be prerequisite for long-term growth and malignant transformation. Thus alterations in CD45 may result in abnormal functioning of the malignant B-1 cells which may further affect the proliferation of, or signaling within, these cells.
Dang
A M
AM
Department of Pathology, UMDNJ/New Jersey Medical School, Newark 07103, USA.
Phillips
J A
JA
Lin
T
T
Raveche
E S
ES
D000818:Animals; D001402:B-Lymphocytes / Q000145:classification / Q000378:metabolism* / Q000473:pathology*; D001483:Base Sequence; D015153:Blotting, Western; D002469:Cell Separation; D005434:Flow Cytometry; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology* / Q000378:metabolism*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB; D008819:Mice, Nude; D008969:Molecular Sequence Data; D012326:RNA Splicing / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011947:Receptors, Antigen, B-Cell; D017493:Leukocyte Common Antigens