Characterization of a B-CLL derived IgM-lambda antibody expressing typical features of a NPAB.
A human IgM-lambda hybridoma (CB-HB) was established from chronic lymphocytic leukaemia (CLL) B-cells. Immunochemical and molecular characterization of the monoclonal antibody (mab) produced by the CB-HB cells offered typical features of natural polyreactive antibodies (NPAPs) found in fetal and healthy adult organisms. In particular, the CB-HB mab reacted with different self and foreign (viral and bacterial) antigens when tested in three independent systems (solid- and fluid-phase ELISA, Western blot) showing binding constants in a range from 1.9 x 10(-7) to 7.5 x 10(-8) mol/l to four antigens chosen. In addition, the CB-HB mab binding could be inhibited by a rabbit polyclonal antiserum specific for a common idiotype (Id 102) on human polyreactive (auto)antibodies. The variable region of the CB-HB mab was found to be encoded by unmutated copies of germline genes. Interestingly, the VH-DP10 (51p1) segment, encoding for the autoantibody-associated G6-cross reactive idiotype frequently expressed on both fetal and malignant B-cells, was found to be used with a V segment (VLO11). Collectively these data imply that cells belonging to the natural polyreactive B-cell repertoire undergo malignant transformation. A stimulation by autoantigens or common foreign antigens may be involved.
Böhme
H
H
Institut für Medizinische Immunologie, Universitätsklinikum Charité, Berlin, Germany.
Seifert
M
M
Roggenbuck
D
D
Döcke
W
W
von Baehr
R
R
Hansen
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001483:Base Sequence; D015153:Blotting, Western; D006801:Humans; D006825:Hybridomas; D007075:Immunoglobulin M / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000276:immunology*; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007146:Immunoglobulin lambda-Chains