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*Substance via MeSH
The Journal of Immunology, 2006, 177: 45-52.
Copyright © 2006 by The American Association of Immunologists

B Cells and Dendritic Cells from V{kappa}8 Light Chain Transgenic Mice Activate MRL-lpr/gld CD4+ T Cells1

Britte C. Beaudette-Zlatanova*, Tina Ling*, Mark J. Shlomchik{ddagger}, Ann Marshak-Rothstein{dagger} and Ian R. Rifkin2,*

* Renal Section, Department of Medicine, and {dagger} Department of Microbiology, Boston University School of Medicine, Boston, MA 02118; {ddagger} Section of Immunobiology and Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520

Autoreactive CD4+ T cells are required for full expression of disease in human systemic lupus erythematosus and in spontaneous murine lupus. However, the Ag specificity of these CD4+ T cells remains largely unknown. Rheumatoid factor (RF) B cells function as highly efficient APCs by taking up immune complexes (IC) and presenting IC constituents to T cells. We hypothesized that Ag-specific CD4+ T cells in lupus-prone mice could be identified by stimulating the CD4+ T cells with RF B cells from AM14 RF BCR transgenic mice pulsed with IC containing lupus-associated autoantibodies and autoantigens. This approach identified several independent T cell lines that proliferated robustly in response to IC-pulsed spleen cells from the AM14 RF BCR transgenic mice. However, these T cells did not recognize an IC constituent. Instead, these T cells recognized a determinant dependent on the inheritance of the transgene-encoded V{kappa}8 L chain, most likely a neoantigen created by the insertion of the transgene into the genome. Additionally, although the precise nature of the neoantigen is not known, the T cells described in this report may provide a useful tool for examining the role of T cells in the RF autoantibody response.







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