B Cell Depletion with Anti-CD79 mAbs Ameliorates Autoimmune Disease in MRL/lpr Mice

Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
The Journal of Immunology (Impact Factor: 4.92). 10/2008; 181(5):2961-72. DOI: 10.4049/jimmunol.181.5.2961
Source: PubMed


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 inflammation. To determine whether B cell depletion by administration of Abs is effective in lupus mice with an intact immune system and established disease, we screened several B cell-specific mAbs and found that a combination of anti-CD79alpha and anti-CD79beta Abs was most effective at depleting B cells in vivo. Anti-CD79 therapy started at 4-5 mo of age in MRL/lpr mice significantly decreased B cells (B220(+)CD19(+)) in peripheral blood, bone marrow, and spleens. Treated mice also had a significant increase in the number of both double-negative T cells and naive CD4(+) T cells, and a decreased relative abundance of CD4(+) memory cells. Serum anti-chromatin IgG levels were significantly decreased compared with controls, whereas serum anti-dsDNA IgG, total IgG, or total IgM were unaffected. Overall, survival was improved with lower mean skin scores and significantly fewer focal inflammatory infiltrates in submandibular salivary glands and kidneys. Anti-CD79 mAbs show promise as a potential treatment for systemic lupus erythematosus and as a model for B cell depletion in vivo.

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Available from: John Cambier, Dec 22, 2014
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    • "MRL-MpJFas lpr (MRL/lpr) mice have a mutation in the Fas gene and develop a disease similar to SLE that is characterised by glomerulonephritis, vasculitis, splenomegaly, hypergammaglobulinemia, and the production of anti-dsDNA antibodies [21]. In this mouse strain, B cell elimination using an anti-CD79 antibody decreased the manifestation of SLE-like symptoms, demonstrating the importance of B cells in SLE physiopathology [22] [23]. B cells develop from hematopoietic stem cells in the bone marrow through a series of differentiation stages. "
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    • "those coupled to potent cytotoxic agents, are effective at killing human B cell lymphoma cells both in vitro and in mouse chimeras (Polson et al. 2007). Anti-mouse CD79 mAbs have also been shown to be effective in depleting B cells and at ameliorating autoimmune disease in MRL/lpr mice (Li et al. 2008). To engineer recombinant anti-CD79 antibodies with additional effector functions in mice, we have cloned and sequenced the full-length IG heavy and light chains of an Armenian hamster (Cricetulus migratorius) anti-mouse CD79B reagent antibody (clone HM79-16 or HM79b) (in the absence of genomic information, this antibody is designated as IgG2, λ1 by the companies which distribute it) (Koyama et al. 1997). "
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