title: Splenic marginal zone lymphoma with VH1-02 gene rearrangement expresses poly- and self-reactive antibodies with similar reactivity.
abstract: 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.
authors: Department of Pathology, University Hospital of Oslo, Oslo, Norway. abdirashid.ali.warsame@radiumhospitalet.no
authors: Abdirashid A
authors: AA
authors: Warsame
authors: Hans-Christian
authors: HC
authors: Aasheim
authors: Kjell
authors: K
authors: Nustad
authors: Gunhild
authors: G
authors: Trøen
authors: Anne
authors: A
authors: Tierens
authors: Vivian
authors: V
authors: Wang
authors: Ulla
authors: U
authors: Randen
authors: Hiep P
authors: HP
authors: Dong
authors: Sverre
authors: S
authors: Heim
authors: Andreas
authors: A
authors: Brech
authors: Jan
authors: J
authors: Delabie
mesh_terms: D000906:Antibodies / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity; D001798:Blood Proteins / Q000276:immunology / Q000378:metabolism; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015321:Gene Rearrangement / Q000276:immunology*; D057809:HEK293 Cells; D016174:Hepacivirus / Q000254:growth & development / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000821:virology; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D016130:Immunophenotyping; D007519:Isoantigens / Q000276:immunology / Q000378:metabolism; D007621:Karyotyping; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013160:Splenic Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014162:Transfection
chemical_list: D000906:Antibodies; D001798:Blood Proteins; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D007519:Isoantigens; D011994:Recombinant Proteins