APRIL Induces a Novel Subset of IgA+ Regulatory B Cells That Suppress Inflammation via Expression of IL-10 and PD-L1

Abstract

Regulatory B cells (Bregs) are immunosuppressive cells that modulate immune responses through multiple mechanisms. The signals required for the differentiation and activation of these cells remain still poorly understood. We have already shown that overexpression of A PRoliferation-Inducing Ligand (APRIL) reduces the incidence and severity of collagen-induced arthritis (CIA) in mice. Furthermore, we have described that APRIL, but not BAFF, promoted IL-10 production and regulatory functions in human B cells. Therefore, we hypothesized that APRIL, but not BAFF, may be involved in the induction and/or activation of IL-10 producing Bregs that suppress inflammatory responses in vitro and in vivo . Here, we describe that APRIL promotes the differentiation of naïve human B cells to IL-10-producing IgA + B cells. These APRIL-induced IgA + B cells display a Breg phenotype and inhibit T cell and macrophage responses through IL-10 and PD-L1. Moreover, APRIL-induced IL-10 producing Bregs suppress inflammation in vivo in experimental autoimmune encephalitis (EAE) and contact hypersensitivity (CHS) models. Finally, we showed a strong correlation between APRIL and IL-10 in the inflamed synovial tissue of inflammatory arthritis patients. Collectively, these observations indicate the potential relevance of this novel APRIL-induced IgA + Breg population for immune homeostasis and immunopathology.

Lactobacillus Casei Zhang Alleviates Shrimp Tropomyosin‐Induced Food Allergy by Switching Antibody Isotypes through the NF‐κB‐Dependent Immune Tolerance

“…[ 52 ] On the other hand, several studies have shown that IgA + memory B cells were increased in allergic children, and IgA + regulatory B cells were also involved in allergic diseases. [ 53,54 ] Therefore, IgA is participated in food allergy but the exact role is not fully understood. In this study, LcZ inhibited IgE production and promoted serum IgA production, the IgA‐producing B cells were also promoted in spleen, which indicated that the strain alleviated allergy not only by directly blocking IgE function but also indirectly through inducing tolerogenic IgA production.…”

Neutrophils at the crossroads of innate and adaptive immunity

“…For example, recently it was found that APRIL promotes the differentiation of naïve human B lymphocytes to IL‐10‐producing IgA + B lymphocytes. These APRIL‐induced IgA + B lymphocytes display a regulatory B cell (Breg) phenotype and inhibit T lymphocyte and macrophage responses through IL‐10 and PD‐L1 199 . Thus, one can imagine that neutrophils can activate B lymphocytes into Breg cells as another way to modulate T lymphocyte functions 200 .…”

High APRIL Levels Are Associated With Slow Disease Progression and Low Immune Activation in Chronic HIV-1-Infected Patients

“…APRIL-stimulated B cells play a regulatory role in T cells to decrease the secretion of TNF-α and IFN-γ from T cells (38). Cynthia et al further reported that APRIL-induced IL-10-producing regulatory B cells (Bregs) dampened inflammation in experimental autoimmune encephalitis (EAE) and contact hypersensitivity (CHS) models (39). A recent study investigating multiple sclerosis (MS) showed that APRIL mediated an anti-inflammatory response in astrocytes by producing IL-10 to suppress antigen-specific T-cell proliferation and pathogenic cytokine secretion.…”