Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation

Hye Mee Joo, Christine Coquery, Yaming Xue, Ingrid Gayet, Stacey R. Dillon, Marilynn Punaro, Gerard Zurawski, Jacques Banchereau, Virginia Pascual, Sang Kon Oh

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN- dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we demonstrate that SLE-DCs can efficiently stimulate naive and memory B cells to differentiate into IgG- and IgA-plasmablasts (PBs) resembling those found in the blood of SLE patients. SLE-DC-mediated IgG-PB differentiation is dependent on B cell-activating factor (BAFF) and IL-10, whereas IgA-PB differentiation is dependent on a proliferation-inducing ligand (APRIL). Importantly, SLE-DCs express CD138 and trans-present CD138-bound APRIL to B cells, leading to the induction of IgA switching and PB differentiation in an IFN-α-independent manner. We further found that this mechanism of providing B cell help is relevant in vivo, as CD138-bound APRIL is expressed on blood monocytes from active SLE patients. Collectively, our study suggests that a direct myeloid DC-B cell interplay might contribute to the pathogenesis of SLE.

Original languageEnglish (US)
Pages (from-to)1335-1348
Number of pages14
JournalJournal of Experimental Medicine
Volume209
Issue number7
DOIs
StatePublished - Jul 2 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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