Interferon-α-induced B-lymphocyte stimulator expression and mobilization in healthy and systemic lupus erthymatosus

Patricia López1, Dagmar Scheel-Toellner2, Javier Rodríguez-Carrio2

  • 1Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain. Department of Functional Biology, Immunology Area, Faculty of Medicine, University of Oviedo, Oviedo, Spain, Rheumatology Research Group, MRC Centre for Immune Regulation, Institute for Biomedical Research, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK and Department of Internal Medicine, Hospital Universitario Central de Asturias, Oviedo, Spain. lopezpatricia@uniovi.es.

Insights

Interferon-alpha and SLE immune complexes increase B-lymphocyte stimulator (BLyS) in monocytes. Active systemic lupus erythematosus (SLE) patients show higher BLyS mobilization and expression in immune cells.

Area of Science:

  • Immunology
  • Rheumatology

Background:

  • Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune system dysregulation.
  • B-lymphocyte stimulator (BLyS) plays a crucial role in B-cell survival and maturation, and its overexpression is implicated in SLE pathogenesis.

Purpose of the Study:

  • To investigate the cellular sources and regulatory factors driving B-lymphocyte stimulator (BLyS) overexpression in SLE patients.
  • To determine the impact of inflammatory cytokines and SLE-specific immune complexes on BLyS expression and mobilization.

Main Methods:

  • Quantification of surface and intracellular BLyS by flow cytometry in healthy and SLE monocytes stimulated with TNF-α, IFN-α, IFN-γ, GM-CSF, and SLE immune complexes (SLE-ICs).
  • Measurement of soluble BLyS by ELISA.
  • Ex vivo analysis of BLyS expression in various immune cell subsets from SLE patients and healthy controls.
  • Assessment of disease activity using the BILAG index.

Main Results:

  • In vitro, IFN-α and SLE-ICs increased surface-bound BLyS in healthy monocytes.
  • SLE monocytes from patients with high anti-dsDNA or disease activity showed enhanced intracellular BLyS, rapid mobilization to the membrane, and release upon IFN-α stimulation.
  • Ex vivo, SLE patients exhibited upregulated BLyS in B cells, myeloid DCs, and plasmacytoid DCs.
  • Active SLE patients displayed an increased surface:intracellular BLyS ratio in monocytes and myeloid DCs.

Conclusions:

  • IFN-α and disease activity/anti-dsDNA levels influence monocyte BLyS induction and mobilization.
  • Active SLE patients show elevated membrane-bound:intracellular BLyS ratios in monocytes and myeloid DCs, indicating increased BLyS release.
  • Widespread BLyS expression in blood cells of SLE patients suggests generalized immune stimulation.
Abstract

Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
14.3K
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K
Cells of the Adaptive Immune Response01:23

Cells of the Adaptive Immune Response

The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
6.8K