Article

B cells as therapeutic targets in SLE

Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA.
Nature Reviews Rheumatology (Impact Factor: 10.25). 06/2010; 6(6):326-37. DOI: 10.1038/nrrheum.2010.68
Source: PubMed

ABSTRACT The use of B-cell targeted therapies for the treatment of systemic lupus erythematosus (SLE) has generated great interest owing to the multiple pathogenic roles carried out by B cells in this disease. Strong support for targeting B cells is provided by genetic, immunological and clinical observations that place these cells at the center of SLE pathogenesis, as initiating, amplifying and effector cells. Interest in targeting B cells has also been fostered by the successful use of similar interventions to treat other autoimmune diseases such as rheumatoid arthritis, and by the initial promise shown by B-cell depletion to treat SLE in early studies. Although the initial high enthusiasm has been tempered by negative results from phase III trials of the B-cell-depleting agent rituximab in SLE, renewed vigor should be instilled in the field by the convergence of the latest results using agents that inhibit B-cell-activating factor (BAFF, also known as BLyS and tumor necrosis factor ligand superfamily, member 13b), further analysis of data from trials using rituximab and greatly improved understanding of B-cell biology. Combined, the available information identifies several new avenues for the therapeutic targeting of B cells in SLE.

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    • "Activity of Human CD20-Specific IgG Subclasses in Humanized Mice Because CD20 is the major target for therapeutic B celldepleting antibodies, we next assessed the CD20 expression pattern on human B cells developing in humanized mice and humans (Johnson and Press, 2000; Sanz and Lee, 2010). As shown in Figure 5A, CD20 was highly expressed on all IgM+ B cell populations in the blood, spleen, and bone marrow of humanized mice. "
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    Cell Reports 03/2014; 7(1). DOI:10.1016/j.celrep.2014.02.041 · 8.36 Impact Factor
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    • "e l s e v i e r . c o m / l o c a t e / b i o c h e m p h a r m erythematosus (SLE) pathogenesis [12] [13] [14]. The B cells with prolonged lifespan are considered culprits in developing lupuslike autoimmune diseases [9,14–16]. "
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    Biochemical pharmacology 11/2013; 87(2). DOI:10.1016/j.bcp.2013.11.006 · 4.65 Impact Factor
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    • "Although the principal mission of B lymphocytes is considered to reside in immunoglobulin pro­ duction, an effector role for these cells in reg­ ulating immune activity has been repeatedly noted (Zouali, 2008). With the recent success of B cell depletion therapy in autoimmune diseases, there is growing evidence that a population of cells contained within the B cell pool expresses immunostimulatory activity and is involved in clinical autoimmunity (Jacob and Stohl, 2010; Perosa et al., 2010; Sanz and Lee, 2010). Yet clear identification of the B cells that possess this function has remained a mystery. "
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