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Research Article Free access | 10.1172/JCI110076

Chronic Lymphocytic Leukemia Cells Lack the 185,000-Dalton Macromolecular Insoluble Cold Globulin Present on Normal B Lymphocytes

Mary A. Simmonds, Gloria Sobczak, and Stephen P. Hauptman

The Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Find articles by Simmonds, M. in: PubMed | Google Scholar

The Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Find articles by Sobczak, G. in: PubMed | Google Scholar

The Cardeza Foundation for Hematologic Research, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

Find articles by Hauptman, S. in: PubMed | Google Scholar

Published March 1, 1981 - More info

Published in Volume 67, Issue 3 on March 1, 1981
J Clin Invest. 1981;67(3):624–631. https://doi.org/10.1172/JCI110076.
© 1981 The American Society for Clinical Investigation
Published March 1, 1981 - Version history
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Abstract

We have recently characterized two lymphocyte-associated membrane proteins which have been termed 225,000-dalton and 185,000-dalton macromolecular insoluble cold globulin (225-MICG and 185-MICG, respectively) to distinguish their major physicochemical properties. These proteins differ antigenically, structurally, and in their cellular distribution. T cells can be distinguished by the synthesis and presence in the plasma membrane of 225-MICG, Null cells by the appearance of 185-MICG, and B cells by the appearance of both 225- and 185-MICG. The characterization of these two proteins in the monoclonal B lymphocytes of chronic lymphocytic leukemia forms the basis of this report.

Using immunofluorescent microscopy, we found only 225-MICG on the surface of chronic lymphocytic leukemia (CLL) cells in 15 patients, whereas control B cells from 20 individuals displayed both 225- and 185-MICG. When MICG proteins were isolated and compared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, normal B cells showed two stained bands, corresponding to 225- and 185-MICG, whereas the CLL cells demonstrated only the 225-MICG band. Using labeled amino acid incorporation into cellular protein, normal B cells were shown to synthesize 225- and 185-MICG, whereas CLL cells synthesized only 225-MICG, as determined by immune or cold precipitation of labeled cell lysates. When labeled secretions from B cells and CLL cells were analyzed by immune precipitation, 225- and 185-MICG were secreted by B cells, whereas neither protein was secreted by CLL cells. When normal B cells and CLL cells were mixed, incubated, and lysed together, both 225- and 185-MICG were present, thus excluding proteolysis as a cause of the absence of 185-MICG in CLL. The lack of 185-MICG in CLL distinguishes leukemic cells from normal B lymphocytes. Furthermore, the absence of this normal cell surface protein in these leukemic cells suggests a role for 185-MICG in the malignant transformation of lymphocytes.

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