IFN-λ is able to augment TLR-mediated activation and subsequent function of primary human B cells

Abstract

During the past decade, increased emphasis has been placed on finding alternatives to IFN-α-based therapies. One such alternative, IFN-λ, has shown therapeutic promise in a variety of diseases, but research of this family of cytokines has been primarily focused on their antiviral activities. The goal of the present study was to investigate the role of IFN-λ in the regulation and modulation of B cell function. We show that, similar to IFN-α, IFN-λ1 is able to augment TLR-mediated B cell activation, partially attributed to an upregulation of TLR7 expression, and that both naïve and memory B cells express the limiting type III IFN receptor component, IFN-λR1. Furthermore, this IFN-λ-enhanced B cell activation resulted in increased cytokine and Ig production during TLR7 challenge, most prominently after the addition of helper T cell signals. Ultimately, these elevated cytokine and Ig levels could be partially attributed to the increase in proliferation of TLR7-challenged B cells by both type I and type III IFNs. These findings demonstrate the ability of IFN-λ to boost humoral immunity, an important attribute to consider for further studies on immunity to pathogens, vaccine development, and ongoing advancement of therapeutic strategies aimed at replacing IFN-α-based treatments with IFN-λ.

Type III Interferons in Hepatitis C Virus Infection

“…Generally, the role of IFN-λ on B cells was only modestly studied. One recent article by de Groen et al demonstrated that both naive and memory B cells express IFNLR1 mRNA and that IFN-λ1 can activate B cells (83). Treatment of B cells with IFN-λ1 led to increased expression of ISGs (Mx1 and OAS1) as well as increased expression of TLR7.…”

“…Finally, IFN-λ1 stimulation increased the proliferation of B cells stimulated with TLR7/8 agonist. However, after TLR2 or TLR9 stimulation, IFN-λ1 had no effect on the antibody production or proliferation (83). Globally, this study suggests that IFN-λ1 can enhance B cell response, but only under certain stimulation conditions.…”

Insights into IL‐29: Emerging role in inflammatory autoimmune diseases

“…CD19 + B cells stimulated with IL‐29 could significantly up‐regulate IFN‐stimulated genes myxovirus resistance‐1 (Mx1) and OAS1 expression. IL‐29 stimulation on CD19 + B cells also up‐regulated TLR7 expression . Intriguingly, the combination of IL‐29 with R848 enhanced TLR7/8‐mediated IgG and IgM production, and the production of R848‐mediated IL‐6 on treated CD19 + B cells, implying the role of IL‐29 to regulate TLR7/8‐triggered cytokine secretion .…”

“…Human CD27 − naive and CD27 + B cells stimulated by IL‐29 alone or in combination with the TLR7/8 ligand R848 significantly up‐regulated the marker CD69, indicating that both naive and memory B cell populations were responsive to IL‐29 stimulation . CD19 + B cells stimulated with IL‐29 could significantly up‐regulate IFN‐stimulated genes myxovirus resistance‐1 (Mx1) and OAS1 expression.…”

“…These mediators are members of a large family called IL‐10 family, composed of nine cytokines: IL‐10, IL‐19, IL‐20, IL‐22, IL‐24, IL‐26, IL‐28A, IL‐28B and IL‐29 . All type III IFNs bind to the same receptor complex consisting of IFN‐LR1 (also named IL‐28R1, CRF2‐12 or LICR) and IL‐10R2 (IL‐10R2 and CRF2‐4) . Recently, IL‐29 has been focused much attention.…”