Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity

• Published in: Blood 2011-09, Vol.118 (12), p.3331-3339
• Main Authors: Warsame, Abdirashid A., Aasheim, Hans-Christian, Nustad, Kjell, Trøen, Gunhild, Tierens, Anne, Wang, Vivian, Randen, Ulla, Dong, Hiep P., Heim, Sverre, Brech, Andreas, Delabie, Jan
• Format: Article
• Language: English
• Subjects: Antibodies - genetics; Antibodies - immunology; Antibodies - metabolism; Antibody Specificity; Biological and medical sciences; Blood Proteins - immunology; Blood Proteins - metabolism; Cloning, Molecular; Enzyme-Linked Immunosorbent Assay; Female; Gene Rearrangement - immunology; HEK293 Cells; Hematologic and hematopoietic diseases; Hepacivirus - growth & development; Hepacivirus - immunology; Hepatitis C - immunology; Hepatitis C - virology; Humans; Immunoglobulin Light Chains - genetics; Immunoglobulin Light Chains - immunology; Immunoglobulin Light Chains - metabolism; Immunoglobulin Variable Region - genetics; Immunoglobulin Variable Region - immunology; Immunoglobulin Variable Region - metabolism; Immunohistochemistry; Immunophenotyping; Isoantigens - immunology; Isoantigens - metabolism; Karyotyping; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell, Marginal Zone - genetics; Lymphoma, B-Cell, Marginal Zone - immunology; Lymphoma, B-Cell, Marginal Zone - pathology; Male; Medical sciences; Middle Aged; Protein Binding; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Recombinant Proteins - metabolism; Spleen - immunology; Spleen - metabolism; Spleen - pathology; Splenic Neoplasms - genetics; Splenic Neoplasms - immunology; Splenic Neoplasms - pathology; Transfection
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-03-341651

One-third of all splenic marginal zone lymphomas (SMZL) use the IgH VH1-02 gene. These cases are usually not associated with hepatitis C virus infection. Of interest, the rearranged VH1-02 genes display similar complementarity determining regions 3, a finding confirmed by our study. The latter suggests that these SMZL may produce antibodies with similar reactivity. We produced recombinant antibodies from 5 SMZL cases with VH1-02 gene rearrangement to study the binding reactivity of these antibodies. Surprisingly, the recombinant antibodies demonstrated poly- and self-reactivity as demonstrated by their reactivity with nuclear, cytoplasmic, as well as membranous antigens expressed by human cells and by reactivity with human serum. This polyreactivity was specific as demonstrated by ELISA. The antibodies did not react with proteins on the cell surface that are induced by apoptosis as shown for antibodies produced by chronic lymphatic leukemia with VH1-02 gene rearrangement. The results indicate that a common subset of SMZL arises from polyreactive B cells, a subset of marginal zone B cells that are important in the immunologic defense against infection.