Expression of CD45 isoforms by Epstein-Barr virus-transformed human B lymphocytes.
CD45 is the most common protein tyrosine phosphatase (PTPase) in the membrane of white blood cells, serving as a potent regulator of lymphocyte activation and signal transduction. While the amino acid sequence of the intracellular domain of the molecule is conserved, that of the extracellular domain occurs in multiple isoforms, each of the result of alternative mRNA splicing. In T lymphocytes, the lowest relative molecular mass (Mr) form, CD45RO, is associated with acquisition of memory function, whereas the highest Mr isoform, CD45RA, occurs in "naive" T cells. Recently, B cells were also found to express CD45RO following in vitro activation. In order to more fully characterize the expression of CD45 on activated B cells, we have studied its appearance on Epstein-Barr virus-transformed (EBV-t) cells and have found heterogeneous expression of CD45RO and CD45RA. CD45RO expression was unstable with eventual loss by some EBV-t lines, and loss followed by reappearance in others. CD45RA and CD45RO varied independently whereas CD45 remained stable and high, suggesting a fluctuation in other CD45 isoforms. Immunostaining for CD45RB indicates that a probable 190-kDa isoform may be responsible for this observation. A similar bidirectional reversible shifting between CD45RA and CD45RO on T-cell lines has also been reported by Rothstein et al. In contrast to some reports on normal B cells, neither CD45RA nor CD45RO expression was associated with PCA-1 expression. Further evidence that these EBV-t lines may not correspond to a well-defined stage of B-cell differentiation is provided by the observation that a disproportionate loss of CD20 compared to CD19 was noted for several lines. The basis for the CD45 isoform switching, or any functional difference(s) in the expressed isoforms, is not yet known for human B cells.
Harry S. Truman Memorial Veterans Administration Hospital, Columbia, Missouri 65201.
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Marty
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Caldwell
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Feldbush
D015703:Antigens, CD / Q000032:analysis*; D018941:Antigens, CD19; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002460:Cell Line; D002472:Cell Transformation, Viral; D004854:Herpesvirus 4, Human; D006649:Histocompatibility Antigens / Q000032:analysis*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D017493:Leukocyte Common Antigens
D015703:Antigens, CD; D018941:Antigens, CD19; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D006649:Histocompatibility Antigens; D007136:Immunoglobulins; D017493:Leukocyte Common Antigens