B cell-specific MHC class II deletion reveals multiple nonredundant roles for B cell antigen presentation in murine lupus

Josephine R. Giles, Michael Kashgarian, Pandelakis A. Koni, Mark J. Shlomchik

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

B cells have both Ab-dependent and Ab-independent functions in systemic autoimmune diseases, including systemic lupus erythematosus (SLE). Ab-independent functions are known to be important, because mice with B cells but no secreted Ig have severe disease. These functions could include roles in lymphoid development, cytokine secretion, and Ag presentation; however, these possibilities have not been directly tested in SLE models. In this study, we show by lineage-specific ablation of MHC class II (MHCII) that B cell Ag presentation plays a nonredundant role in CD4+ T cell activation and effector differentiation in the MRL.Faslpr mouse model of SLE. MHCII-mediated interactions between B and T cells further promote B cell proliferation and differentiation, and, in fact, inefficient MHCII deletion on B cells led to strong selection of escaped cells in activated and plasmablast compartments, further underscoring the central role of B cell Ag presentation. Despite the leakiness in the system, B cell-specific MHCII deletion resulted in substantially ameliorated clinical disease. Hence, B cell Ag presentation is critical for T and B cell activation and differentiation, as well as target organ damage.

Original languageEnglish (US)
Pages (from-to)2571-2579
Number of pages9
JournalJournal of Immunology
Volume195
Issue number6
DOIs
StatePublished - Sep 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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