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  • 1
    Publication Date: 1990-08-01
    Description: CD5+ B lymphocytes have been postulated to be primarily involved in autoantibody production. To investigate whether CD5 B lymphocytes from chronic lymphocytic leukemia (CLL) patients display the same function, we fused B lymphocytes from 23 CD5+ B-CLL with nonsecreting murine myeloma X-63 cells. Hybrids were derived from 18 of the 23 patients, but only hybrids from 13 patients were found to secrete immunoglobulin (Ig) (IgM kappa 4, IgM lambda 8, and only kappa light chain 1). Supernatants of these hybrids were tested against an extensive panel of antigens by enzyme-linked immunosorbent assay, indirect immunofluorescence, and hemagglutination. At the same time, peripheral blood mononuclear cells (PBMC) from 15 of these patients, including most patients from whom secreting hybrids had not been obtained, were stimulated with phorbol myristate acetate (PMA). Our results indicated that secreting heterohybrids from CLL B lymphocytes are frequently obtained; however, this is highly dependent on the light chain phenotype, since 8 of 9 lambda-expressing CLL produced hybrids secreting complete Igs, as compared with 4 of 12 kappa-expressing CLL. In addition, B lymphocytes of most patients from whom we failed to derive secreting hybrids also failed to secrete Ig on PMA stimulation. Secondly, CD5+ B-CLL lymphocytes were frequently committed to the production of natural autoantibodies, since in 8 of 15 cases (including hybrids and PMA stimulation) anti-Fc activity was found; three of these also displayed a multispecific binding pattern.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 2
    Publication Date: 1990-04-01
    Description: We studied the expression of CD5 and immunoglobulin variable gene families in a panel of monoclonal Epstein-Barr virus (EBV) transformed lines, chronic lymphocytic leukemias (CLLs) and CD5+ and CD5- B-cell lymphomas. The CD5 gene expression was in all cases identical to that of T-cell malignancies. The utilization of the various VH and VK gene families was roughly proportional to the estimated gene family size in EBV lines obtained from adult healthy subjects. In contrast we found a statistically significant biased usage of VH6 in CLL and VH5 in CD5+ lymphomas as compared with EBV lines, and of VKIII in both CLL and CD5+ lymphomas as compared with EBV lines. Some differences in the variable gene usage were also noted when comparing CD5+ and CD5- lymphomas. These findings are analyzed in the context of possible mechanisms involved in the malignant transformation of CD5+ B cells.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 3
    Publication Date: 1990-08-01
    Description: CD5+ B lymphocytes have been postulated to be primarily involved in autoantibody production. To investigate whether CD5 B lymphocytes from chronic lymphocytic leukemia (CLL) patients display the same function, we fused B lymphocytes from 23 CD5+ B-CLL with nonsecreting murine myeloma X-63 cells. Hybrids were derived from 18 of the 23 patients, but only hybrids from 13 patients were found to secrete immunoglobulin (Ig) (IgM kappa 4, IgM lambda 8, and only kappa light chain 1). Supernatants of these hybrids were tested against an extensive panel of antigens by enzyme-linked immunosorbent assay, indirect immunofluorescence, and hemagglutination. At the same time, peripheral blood mononuclear cells (PBMC) from 15 of these patients, including most patients from whom secreting hybrids had not been obtained, were stimulated with phorbol myristate acetate (PMA). Our results indicated that secreting heterohybrids from CLL B lymphocytes are frequently obtained; however, this is highly dependent on the light chain phenotype, since 8 of 9 lambda-expressing CLL produced hybrids secreting complete Igs, as compared with 4 of 12 kappa-expressing CLL. In addition, B lymphocytes of most patients from whom we failed to derive secreting hybrids also failed to secrete Ig on PMA stimulation. Secondly, CD5+ B-CLL lymphocytes were frequently committed to the production of natural autoantibodies, since in 8 of 15 cases (including hybrids and PMA stimulation) anti-Fc activity was found; three of these also displayed a multispecific binding pattern.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    Publication Date: 1991-08-01
    Description: Previous work with monoclonal Igs (MIgs) has demonstrated that a high proportion of paraproteins bind to self-antigens such as the Fc fragment of IgG, Ii blood group antigens, cytoskeleton proteins, DNA, and myelin-associated glycoprotein (MAG). Recent work in CLL indicates that CD5+ B lymphocytes are frequently committed to production of autoantibodies. We have examined the antibody specificity of MIgs derived from the tumor cells of 31 different patients with CD5- B-cell lymphomas. Our results indicate that the tumor cells from 8 of these 31 patients (25.8%) express Igs with autoantibody activity. In two cases antibody activity was multispecific. In four cases, antibody activity was exclusively directed against the Fc fragment of IgG, whereas the two other cases bound to both Fc fragment of IgG and nuclear antigens. Most non-Hodgkin's lymphomas (NHL) are derived from CD5- B cells. These results indicate that like CLL, NHL also express Igs that frequently have autoantibody activity.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Publication Date: 1996-06-01
    Description: Human natural “anti-Gal” antibodies are specifically directed to Gal alpha 1–3Gal beta 1–4GlcNAc residues expressed on non-primate mammal and new world monkey cells. We investigated the relative involvement of purified IgG and IgM anti-Gal as xenoreactive natural antibodies (XNA). IgG and IgM were isolated from human plasma, and anti-Gal antibodies were purified by affinity chromatography on a Synsorb-14 column (Chembiomed, Edmonton, Alberta, Canada). Anti-Gal of both IgM and IgG classes represent the bulk of human XNA that bind to porcine platelets in enzyme-linked immunosorbent assay (ELISA). On immunoblots, normal human sera, as well as purified IgM and IgG fractions, reacted with 115- , 125-, 135-, 150-, 180-, 210-, and 240-kd) pig platelet proteins, whereas purified anti-Gal antibodies of both IgM and IgG classes mainly bound to 135-, 150-, 180-, and 210-kD glycoproteins. A low reactivity was observed in ELISA with anti-Gal free IgM and IgG, indicating that xenoantibodies are not solely directed to galactosyl epitopes. These antibodies revealed bands of 115, 125, and 240 kD, alpha-Galactosidase treatment of porcine platelet glycoproteins (gps) enriched by affinity chromatography abrogated the reactivity of 135- and 210-kD proteins. N- and O-glycosidase treatments demonstrated that alpha-galactosyl residues are located on the O-glycans of the 135-kD component. Finally, glycoproteins of 90 and 135 kD were identified by amino acid sequencing as the pig analogs of the human glycoproteins IIIa and IIb, respectively, whereas the 240-kD) component was identified as the porcine fibrinogen, using a new murine monoclonal antibody (naM147–7B6; IgG1) specific for its beta-chain.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 6
    Publication Date: 1990-04-01
    Description: We studied the expression of CD5 and immunoglobulin variable gene families in a panel of monoclonal Epstein-Barr virus (EBV) transformed lines, chronic lymphocytic leukemias (CLLs) and CD5+ and CD5- B-cell lymphomas. The CD5 gene expression was in all cases identical to that of T-cell malignancies. The utilization of the various VH and VK gene families was roughly proportional to the estimated gene family size in EBV lines obtained from adult healthy subjects. In contrast we found a statistically significant biased usage of VH6 in CLL and VH5 in CD5+ lymphomas as compared with EBV lines, and of VKIII in both CLL and CD5+ lymphomas as compared with EBV lines. Some differences in the variable gene usage were also noted when comparing CD5+ and CD5- lymphomas. These findings are analyzed in the context of possible mechanisms involved in the malignant transformation of CD5+ B cells.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 7
    Publication Date: 1991-08-01
    Description: Previous work with monoclonal Igs (MIgs) has demonstrated that a high proportion of paraproteins bind to self-antigens such as the Fc fragment of IgG, Ii blood group antigens, cytoskeleton proteins, DNA, and myelin-associated glycoprotein (MAG). Recent work in CLL indicates that CD5+ B lymphocytes are frequently committed to production of autoantibodies. We have examined the antibody specificity of MIgs derived from the tumor cells of 31 different patients with CD5- B-cell lymphomas. Our results indicate that the tumor cells from 8 of these 31 patients (25.8%) express Igs with autoantibody activity. In two cases antibody activity was multispecific. In four cases, antibody activity was exclusively directed against the Fc fragment of IgG, whereas the two other cases bound to both Fc fragment of IgG and nuclear antigens. Most non-Hodgkin's lymphomas (NHL) are derived from CD5- B cells. These results indicate that like CLL, NHL also express Igs that frequently have autoantibody activity.
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Location Call Number Expected Availability
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