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Publication Detail
Selective targeting of B cells with agonistic anti-CD40 is an efficacious strategy for the generation of induced regulatory T2-like B cells and for the suppression of lupus in MRL/lpr mice.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Blair PA, Chavez-Rueda KA, Evans JG, Shlomchik MJ, Eddaoudi A, Isenberg DA, Ehrenstein MR, Mauri C
  • Publication date:
  • Pagination:
    3492, 3502
  • Journal:
    J Immunol
  • Volume:
  • Issue:
  • Status:
  • Country:
    United States
  • Language:
  • Keywords:
    Animals, Antibodies, Monoclonal, B-Lymphocyte Subsets, CD40 Antigens, Cell Differentiation, Cell Proliferation, Cells, Cultured, Lupus Erythematosus, Systemic, Lymphocyte Count, Mice, Mice, Inbred C57BL, Mice, Inbred MRL lpr, Mice, Transgenic, Th1 Cells
We have previously reported that IL-10(+) regulatory B cells, known to play an important role in controlling autoimmunity and inflammatory disorders, are contained within the transitional 2 immature (T2) B cell pool (T2 Bregs). Therapeutic strategies facilitating their enrichment or enhancing their suppressive activity are highly attractive. In this study, we report that agonistic anti-CD40 specifically targets T2 B cells and enriches Bregs upon short-term in vitro culture. Although transfer of unmanipulated T2 B cells, isolated from mice with established lupus, failed to confer protection to diseased mice, transfer of in vitro anti-CD40-generated T2 B cells (T2-like-Bregs) significantly improved renal disease and survival by an IL-10-dependent mechanism. T2-like-Bregs readily accumulated in the spleen after transfer, suppressed Th1 responses, induced the differentiation of IL-10(+)CD4(+)T cells, and conveyed a regulatory effect to CD4(+)T cells. In addition, in vivo administration of agonistic anti-CD40, currently on trial for the treatment of cancer, halted and reversed established lupus. Taken together, our results suggest a novel cellular approach for the amelioration of experimental lupus.
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