title: Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors.
abstract: The pathogenesis of Chlamydophila psittaci-negative ocular adnexal extranodal marginal zone lymphomas (OAEMZLs) is poorly understood. OAEMZLs are monoclonal tumors expressing a biased repertoire of mutated surface immunoglobulins. Antigenic activation of the B-cell receptor (BCR) may have a role in the pathogenesis of these lymphomas. We have analyzed the reactivity of recombinant OAEMZL immunoglobulins. OAEMZL antibodies reacted with self-human antigens, as demonstrated by enzyme-linked immunosorbent assays, HEp-2 immunofluorescence and human protein microarrays. All the analyzed recombinant antibodies (rAbs) exhibited polyreactivity by comprehensive protein array antibody reactivity and some rAbs also demonstrated rheumatoid factor activity. The identity of several reactive antigens was confirmed by microcapillary reverse-phase high-performance liquid chromatography nano-electrospray tandem mass spectrometry. The tested rAbs frequently reacted with shared intracellular and extracellular self-antigens (for example, galectin-3). Furthermore, these self-antigens induced BCR signaling in B cells expressing cognate surface immunoglobulins derived from OAEMZLs. These findings indicate that interactions between self-antigens and cognate OAEMZL tumor-derived BCRs are functional, inducing intracellular signaling. Overall, our findings suggest that self-antigen-induced BCR stimulation may be implicated in the pathogenesis of C. psittaci-negative OAEMZLs.
authors: Division of Hematology and Oncology, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors: D
authors: D
authors: Zhu
authors: 1] Division of Hematology and Oncology, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA [2] Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
authors: S
authors: S
authors: Bhatt
authors: Division of Hematology and Oncology, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors: X
authors: X
authors: Lu
authors: Division of Hematology and Oncology, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA.
authors: F
authors: F
authors: Guo
authors: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors: H
authors: H
authors: Veelken
authors: Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, CA, USA.
authors: D K
authors: DK
authors: Hsu
authors: 1] Department of Dermatology, School of Medicine, University of California-Davis, Sacramento, CA, USA [2] Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC [3] Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors: F-T
authors: FT
authors: Liu
authors: Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: S
authors: S
authors: Alvarez Cubela
authors: Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: K
authors: K
authors: Kunkalla
authors: Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: F
authors: F
authors: Vega
authors: Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA.
authors: J R
authors: JR
authors: Chapman-Fredricks
authors: 1] Division of Hematology and Oncology, Department of Medicine, University of Miami, Sylvester Comprehensive Cancer Center, Miami, FL, USA [2] Department of Molecular and Cellular Pharmacology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
authors: I S
authors: IS
authors: Lossos
mesh_terms: D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D002691:Chlamydophila psittaci; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005134:Eye Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D040081:Protein Array Analysis; D009956:Psittacosis / Q000382:microbiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology; D021241:Spectrometry, Mass, Electrospray Ionization; D014407:Tumor Cells, Cultured
chemical_list: D001324:Autoantigens; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins