B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice

Yongmei Li, Fangqi Chen, Mary Putt, Yumee K. Koo, Michael P. Madaio, John C. Cambier, Philip L. Cohen, Robert A. Eisenberg

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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-CD79α and anti-CD79β 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.

Original languageEnglish (US)
Pages (from-to)2961-2972
Number of pages12
JournalJournal of Immunology
Volume181
Issue number5
DOIs
StatePublished - Sep 1 2008

Fingerprint

Inbred MRL lpr Mouse
Autoimmune Diseases
B-Lymphocytes
T-Lymphocytes
Systemic Lupus Erythematosus
CD95 Antigens
Kidney
Genetic Loci
Submandibular Gland
Immune System Diseases
Salivary Glands
Serum
Autoantibodies
Chromatin
Immunoglobulin M
Spleen
Immunoglobulin G
Bone Marrow
Inflammation
Skin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Li, Y., Chen, F., Putt, M., Koo, Y. K., Madaio, M. P., Cambier, J. C., ... Eisenberg, R. A. (2008). B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice. Journal of Immunology, 181(5), 2961-2972. https://doi.org/10.4049/jimmunol.181.5.2961

B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice. / Li, Yongmei; Chen, Fangqi; Putt, Mary; Koo, Yumee K.; Madaio, Michael P.; Cambier, John C.; Cohen, Philip L.; Eisenberg, Robert A.

In: Journal of Immunology, Vol. 181, No. 5, 01.09.2008, p. 2961-2972.

Research output: Contribution to journalArticle

Li, Y, Chen, F, Putt, M, Koo, YK, Madaio, MP, Cambier, JC, Cohen, PL & Eisenberg, RA 2008, 'B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice', Journal of Immunology, vol. 181, no. 5, pp. 2961-2972. https://doi.org/10.4049/jimmunol.181.5.2961
Li, Yongmei ; Chen, Fangqi ; Putt, Mary ; Koo, Yumee K. ; Madaio, Michael P. ; Cambier, John C. ; Cohen, Philip L. ; Eisenberg, Robert A. / B cell depletion with anti-CD79 mAbs ameliorates autoimmune disease in MRL/lpr mice. In: Journal of Immunology. 2008 ; Vol. 181, No. 5. pp. 2961-2972.
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