Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

• Published in: Leukemia 2015-07, Vol.29 (7), p.1587-1599
• Main Authors: Zhu, D, Bhatt, S, Lu, X, Guo, F, Veelken, H, Hsu, D K, Liu, F-T, Alvarez Cubela, S, Kunkalla, K, Vega, F, Chapman-Fredricks, J R, Lossos, I S
• Format: Article
• Language: English
• Subjects: 13/109; 13/31; 14/63; 45/23; 45/77; 631/154/51/1568; 631/250/1619/40/1774; 631/67/1990/291/1621/1915; 692/420/2780; 692/699/67/1990/291; 82/1; 82/51; 82/83; Antibodies; Antigen (tumor-associated); Antigen-antibody reactions; Antigens; Autoantigens; Autoantigens - immunology; B cells; B-cell receptor; B-Lymphocytes - immunology; Blotting, Western; Cancer; Cancer Research; Care and treatment; Cell activation; Cell receptors; Chlamydophila psittaci; Chromatography, High Pressure Liquid; Critical Care Medicine; Development and progression; Diagnosis; Enzyme-Linked Immunosorbent Assay; Enzymes; Eye Neoplasms - immunology; Eye Neoplasms - metabolism; Eye Neoplasms - pathology; Fluorescent Antibody Technique; Galectin-3; Genes; Genetic aspects; Health aspects; Hematology; High performance liquid chromatography; Humans; Immunoassays; Immunoenzyme Techniques; Immunofluorescence; Immunoglobulins; Immunoprecipitation; Infections; Inflammation; Intensive; Internal Medicine; Intracellular; Intracellular signalling; Leukemia; Liquid chromatography; Lymphocytes B; Lymphoma; Lymphoma, B-Cell, Marginal Zone - immunology; Lymphoma, B-Cell, Marginal Zone - metabolism; Lymphoma, B-Cell, Marginal Zone - pathology; MALT lymphoma; Mass spectrometry; Mass spectroscopy; Medicine; Medicine & Public Health; Non-Hodgkin's lymphomas; Oncology; original-article; Pathogenesis; Protein Array Analysis; Protein arrays; Proteins; Psittacosis - microbiology; Receptors; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Recombinant Proteins - immunology; Rheumatoid factor; Signaling; Spectrometry, Mass, Electrospray Ionization; Tumor Cells, Cultured; Tumors
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2015.39

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.