Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation. Academic Article uri icon

Overview

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.

publication date

  • June 11, 2012

Research

keywords

  • Cell Differentiation
  • Lupus Erythematosus, Systemic
  • Monocytes
  • Plasma Cells

Identity

PubMed Central ID

  • PMC3405503

Scopus Document Identifier

  • 84864296905

Digital Object Identifier (DOI)

  • 10.1084/jem.20111644

PubMed ID

  • 22689824

Additional Document Info

volume

  • 209

issue

  • 7