Objective. B-1 cells have long been suggested to play an important role in lupus. However, reports to date have been controversial regarding their pathogenic or protective roles in different animal models. We undertook this study to investigate a novel subpopulation of B-1 cells and its roles in murine lupus.Methods. Lymphocyte phenotypes were assessed by flow cytometry. Autoantibody secretion was analyzed by enzyme-linked immunosorbent assay, autoantigen proteome array, and antinuclear antibody assay. Conclusion. Our findings identify a novel subpopulation of B-1 cells that is enriched for autoreactive specificities, undergoes isotype switch, manifests enhanced antigen presentation, promotes Th17 cell differentiation, and is preferentially associated with the development of lupus in a murine model. Together, these findings suggest that L2pB1 cells have the potential to initiate autoimmunity through serologic and T cellmediated mechanisms.

The immunopathogenesis of BD is believed to be T cell-mediated. The objective of this study was to characterize the activation stage and cytokine profile of peripheral blood lymphocytes (PBL), with particular emphasis on gammadelta T cells. Venous blood was collected from 20 patients with BD, and for comparison, from 11 patients with RAS and from 15 healthy controls. Both the expression of activation markers (CD25, CD29, CD40 ligand, CD69 and HLA-DR) on freshly isolated PBL and T cell subsets, and the expression of intracellular cytokines (IL-4, IL-10, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)) on mitogen-stimulated PBL and T cell subsets were analysed by double immunofluorescent staining and flow cytometry. Significantly decreased proportion of alphabeta T cells and increased proportion of gammadelta T cells, CD56+ cells and CD8+ gammadelta T cells were found in BD patients compared with healthy controls. This was also seen to a lesser extent in patients with RAS. Furthermore, in BD a significantly increased proportion of the gammadelta T cell population expressed CD69 and high levels of CD29 and were induced to produce IFN-gamma and TNF-alpha compared with healthy controls. In contrast, an increased percentage of gammadelta T cells from RAS patients was induced to produce IFN-gamma, but not TNF-alpha. These results indicate that in BD, activated gammadelta T cells, capable of producing IFN-gamma and TNF-alpha, are present in peripheral blood, suggesting that gammadelta T cells are dynamic and may be regulating immunopathogenic events.

The thymus is the primary site for T cell development. Within the medulla of the thymus, negative selection of immature T cells causes a large number of cells to undergo apoptosis, appropriately deeming this thymic region a “grave yard.” In observing the thymus medulla of BXSB mice, we noted a significant increase of B cells in lupus-symptomatic males as compared to female controls or lupus- asymptomatic males. Composition analysis of these thymic B cells revealed that both B1 and B2 cells are present. Immunohistochemistry analysis suggests possible chemo-attraction for B cells in the medullar of the thymus due to the expression of CXCL13 in lupus male mice, but not control females. In vivo tracking of peritoneal B cells over a two-week time period indicated that some of the thymic B cells originated from the peritoneal cavity. To test the possible influence of B cells on thymic T cell development, we co-cultured peritoneal and spleen B cells with thymocytes in a 3D hanging drop plate. Our results suggest a “guardian angel” effect by B1 B cells, depicting an enhanced central tolerance by thymic-migration and promoting regulatory T cell survival.