1. Nonstereotyped lymphoma B cell receptors recognize vimentin as a shared autoantigen
- Author
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Harry W. Schroeder, Soung Chul Cha, Jinsong Wei, Amber U Luong, Juliana Ong, Seema Rawal, Shibichakravarthy Kannan, Weiguo Wu, Benjamin Kwak, Kunhwa Kim, Sang Kim, Flavio Egidio Baio, Daniel S. Paick, Michael Popescu, Larry W. Kwak, Sattva S. Neelapu, Richard E. Davis, Leticia S. Watkins, and Hong Qin
- Subjects
Lymphoma, B-Cell ,T-Lymphocytes ,Immunology ,B-cell receptor ,Molecular Sequence Data ,Follicular lymphoma ,Receptors, Antigen, B-Cell ,Vimentin ,macromolecular substances ,Autoantigens ,Epitope ,Article ,Cell Line, Tumor ,medicine ,Immunology and Allergy ,Humans ,Amino Acid Sequence ,Lymphoma, Follicular ,B cell ,Tumor microenvironment ,B-Lymphocytes ,biology ,Antibodies, Monoclonal ,medicine.disease ,Lymphoma ,medicine.anatomical_structure ,Immunoglobulin M ,Immunoglobulin G ,biology.protein ,Cancer research ,Mantle cell lymphoma ,Multiple Myeloma - Abstract
Antigen activation of the B-cell receptor (BCR) may play a role in the pathogenesis of human follicular lymphoma (FL) and other B-cell malignancies. However, the nature of the antigen(s) recognized by tumor BCRs has not been well studied. Here, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL immunoglobulins (Igs) recognized vimentin as a shared autoantigen. The epitope was localized to the N-terminal region of vimentin for all vimentin-reactive tumor Igs. We confirmed specific binding to vimentin by using recombinant vimentin and by performing competitive inhibition studies. Furthermore, using indirect immunofluorescence staining, we showed that the vimentin-reactive tumor Igs colocalized with an anti-vimentin monoclonal antibody in HEp-2 cells. The reactivity to N-terminal vimentin of IgG FL Igs was significantly higher than that of IgM FL Igs (30.4% vs. 10%; P=0.0022). However, vimentin-reactive FL Igs did not share complimentarity determining region 3 motifs and were not homologous. Vimentin was expressed in the T-cell rich regions of FL, suggesting that vimentin is available for binding with tumor BCRs within the tumor microenvironment. Vimentin was also frequently recognized by mantle cell lymphoma and multiple myeloma Igs. Our results demonstrate that vimentin is a shared autoantigen recognized by nonstereotyped FL BCRs and by the Igs of mantle cell lymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B-cell malignancies. These findings may lead to better understanding of the biology and natural history of FL and other B cell malignancies.
- Published
- 2013