Molecular characterization of the CD5 B cell subset: Involvement in autoimmunity and malignancy.
Item
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Title
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Molecular characterization of the CD5 B cell subset: Involvement in autoimmunity and malignancy.
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Identifier
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AAI9020785
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identifier
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9020785
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Creator
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Mayer, Raoul.
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Contributor
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Adviser: Constantin A. Bona
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Date
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1990
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology | Health Sciences, Medicine and Surgery | Biology, Genetics
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Abstract
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CD5 is a pan T lymphocyte cytodifferentiation antigen detected on a small but distinct subset of B lymphocytes in both mice and humans. Studies conducted in both species have suggested that the CD5{dollar}\sp{lcub}+{rcub}{dollar} B cells are of a "young" phenotype, play a major role in the production of autoantibodies and preferentially undergo transformation events leading to the development of certain kinds of B cell malignancies.;Molecular studies were conducted in the murine hybridoma system which allowed the correlation of the CD5 phenotype (CD5{dollar}\sp{lcub}+{rcub}{dollar} or CD5{dollar}\sp{lcub}-{rcub}{dollar}) with immunoglobulin variable gene utilization and fine antigenic specificity. The transcription of the CD5 gene (Ly-1 in mice) was used for the phenotypic assignment of the hybridomas studied. Among a panel of 140 hybridomas producing autoantibodies, which were obtained from various normal and autoimmune prone mice, the expression of the Ly-1 gene was detected in a large fraction of hybridomas obtained from NZB and viable motheaten mice. It is important to note that both of these strains are autoimmune prone have an increased proportion of Ly-1 B cells as compared to normal strains. Ly-1 transcripts were also detected in a large fraction of hybridomas producing DNA specific autoantibodies and a smaller fraction of hybridomas producing rheumatoid factors and multispecific autoantibodies. These results firmly establish a major contribution of the Ly-1 B cell subset to the production of DNA specific autoantibodies and a smaller contribution to the production of rheumatoid factors and "natural" multispecific autoantibodies. The transcription of the Ly-1 gene was different in B cells and B cell hybridomas as compared to T cells. Finally, the hybridoma Ly-1 transcripts were proven to be functional in Western blotting and immunofluorescence studies.;The expression of the CD5 gene was also studied in a panel of human EBV transformed lines, chronic lymphocytic leukemias, B cell lymphomas and T cell malignancies. The transcription of the human CD5 gene was proven to be identical in all cases. The study of the utilization of human immunoglobulin V{dollar}\sb{lcub}\rm H{rcub}{dollar} and V{dollar}\sb{lcub}\rm k{rcub}{dollar} families was conducted in a large panel of chronic lymphocytic leukemias, CD5{dollar}\sp{lcub}+{rcub}{dollar} lymphomas (small lymphocytic lymphomas) and CD5{dollar}\sp{lcub}-{rcub}{dollar} lymphomas and was compared to the immunoglobulin variable gene utilization of a panel of human EBV lines. A statistically significant biased usage of VH{dollar}\sb{lcub}6{rcub}{dollar} was detected in chronic lymphocytic leukemias, VH{dollar}\sb{lcub}5{rcub}{dollar} in CD5{dollar}\sp{lcub}+{rcub}{dollar} lymphomas and V{dollar}\sb{lcub}\rm K{rcub}{dollar}III in both chronic lymphocytic leukemias and CD5{dollar}\sp{lcub}+{rcub}{dollar} lymphomas some differences of V gene utilization were also observed between CD5{dollar}\sp{lcub}+{rcub}{dollar} and CD5{dollar}\sp{lcub}-{rcub}{dollar} lymphomas.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
