Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation.
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.
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Hyemee
H
Joo
Christine
C
Coquery
Yaming
Y
Xue
Ingrid
I
Gayet
Stacey R
SR
Dillon
Marilynn
M
Punaro
Gerard
G
Zurawski
Jacques
J
Banchereau
Virginia
V
Pascual
Sangkon
S
Oh
D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology / Q000494:pharmacology; D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D044967:Serum / Q000276:immunology; D053668:Syndecan-1 / Q000276:immunology / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
D001323:Autoantibodies; D053264:B-Cell Activating Factor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D053668:Syndecan-1; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D016753:Interleukin-10