Nonstereotyped Lymphoma B Cell Receptors Recognize Vimentin as a Shared Autoantigen.

Mar 2012

Cha SC, Qin H, Kannan S, Rawal S, Watkins LS, Baio FE, Wu W, Ong J, Wei J, Kwak B, Kim S, Popescu MS, Paick DS,Kim K, Luong A, Davis RE, Schroeder HW Jr, Kwak LW, Neelapu SS.

Source

Division of Cancer Medicine, Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030;

Abstract

Ag activation of the BCR may play a role in the pathogenesis of human follicular lymphoma (FL) and other B cellmalignancies. However, the nature of the Ag(s) recognized by tumor BCRs has not been well studied. In this study, we used unbiased approaches to demonstrate that 42 (19.35%) of 217 tested FL 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 mAb 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 versus 10%; p = 0.0022). However, vimentin-reactive FL Igs did not share CDR3 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 celllymphoma and multiple myeloma and suggest that vimentin may play a role in the pathogenesis of multiple B cellmalignancies. These findings may lead to a better understanding of the biology and natural history of FL and other B cell malignancies.

PubMed