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Continued antibody gene rearrangement, termed receptor editing, is an important mechanism of central B cell tolerance that may be defective in some autoimmune individuals. We describe a quantitative assay for recombining sequence (RS) rearrangement that we use to estimate levels of antibody light chain receptor editing in various B cell populations. RS(More)
MicroRNAs (miRNAs) have been implicated in B cell lineage commitment, regulation of T cell differentiation, TCR signalling, regulation of IFN signalling, and numerous other immunological processes. However, their function in autoimmunity, and specifically in systemic lupus erythematosus (SLE), remains poorly understood. B6.Sle123 is a spontaneous genetic(More)
Many of the available books on Agile methods and techniques discuss the topic of software debt, especially the importance of managing technical debt on Agile programs. This book turns that relationship around and puts the emphasis on the software debt aspects, while retaining a strong and continuous tie back to Agile methods. The introduction starts with a(More)
TNF-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily, is a prominent inducer of proinflammatory cytokines in vitro and in vivo. We previously found that kidney cells display the TWEAK receptor Fn14, and that TWEAK stimulation of mesangial cells and podocytes induces a potent proinflammatory response. Several of the cytokines(More)
The chronic graft-versus-host (cGVH) reaction results in a syndrome that closely resembles sys-temic lupus erythematosus (SLE). It is induced in nonautoimmune mice by the transfer of allore-active T cells. The availability of anti-DNA transgenes allows us to study the genetic origins of autoantibodies in this model. We induced cGVH in two anti-DNA H chain(More)
Anti-dsDNA Abs are specific diagnostic markers of systemic lupus erythematosus, and are also implicated in kidney pathology. Anti-dsDNA B cells have been shown to be tolerized in nonautoimmune mice. The immunodysregulation that causes these cells to break tolerance is presumably part of the fundamental defects in systemic lupus erythematosus. To explore(More)
MRL/lpr mice develop a spontaneous systemic lupus erythematosus-like autoimmune syndrome due to a dysfunctional Fas receptor, with contributions from other less well-defined genetic loci. The removal of B cells by genetic manipulation not only prevents autoantibody formation, but it also results in substantially reduced T cell activation and kidney(More)
Systemic lupus erythematosus is characterized by production of autoantibodies and glomerulonephritis. The murine chronic graft-vs-host (cGVH) model of systemic lupus erythematosus is induced by allorecognition of foreign MHC class II determinants. Previous studies have shown that cGVH could not be induced in CD4 knockout (CD4KO) mice. We have further(More)
The efficacy of influenza vaccination in patients treated with rituximab is a clinically important question. Rheumatology clinics are populated with patients receiving rituximab for a broad array of disorders. Although several studies have explored the efficacy of other vaccines in rituximab-treated populations, results have been conflicting. We wished to(More)
The Mer receptor tyrosine kinase mediates apoptotic cell phagocytosis and modulates macrophage cytokine production. Mer(-/-) mice have defective clearance of apoptotic debris and develop a systemic lupus erythematosus-like autoimmune syndrome. It was surprising then that B6-Mer(-/-) recipients of bm12 spleen cells failed to develop anti-dsDNA and(More)