SLE: Imbalance in Autoregulation and Feedback Affects B-Cell Lineage Differentiation

HealthDay News –  Researchers have found evidence that an imbalance in the auto-regulatory feedback loop between regulatory B cells and plasma dendritic cells may play a role in the pathogenesis of SLE, and could be a mechanism for future pharmacotherapeutic intervention, according to research published in the journal Immunity.

The findings are based on blood samples from nearly 100 healthy volunteers and 200 patients with SLE.

The team found that SLE patients had an imbalance among three types of immune cells: B cells that produce antibodies; regulatory B cells that help suppress excessive immune responses; and plasmacytoid dendritic cells that produce interferon (IFN)-α. 

A lack of anti-inflammatory B cells leads to overproduction of interferon-α. That, in turn, boosts that number of antibody-producing B cells and suppresses the division and appearance of regulatory B cells, according to the researchers.

The findings could help in developing new SLE therapies, senior researcher Claudia Mauri, PhD, told HealthDay. Mauri is a professor of immunology at University College London. “We will continue to work to develop new [treatment] strategies that harness the anti-inflammatory B cells in patients with SLE,” she said.

Summary and Clinical Applicability

The study suggests that IFN-α concentrations are a key controlling factor regulating whether an immature B cell will develop into a regulatory B cell versus a plasmoblast.   High concentrations of IFN-α tend to drive immature B cells towards differentiation into plasma cells. Feedback between regulatory B cells and plasma dendtritic cells plays an important role in regulating in immune responses.  The researchers suggest that an imbalance in this auto-regulatory feedback loop may play a role in the pathogenesis of SLE, and could be a mechanism for future pharmacotherapeutic intervention.

The authors state that “rituximab therapy might work, in part, by resetting the outcome of the [regulatory B cell-plasma dendritic cell] interaction. Thus, modulation of the feedback loop between plasma dendritic cells and [regulatory B] cells could potentially create new opportunities for immune-based therapies.

Reference

Menon M, Blair PA, Isenberg DA, Mauri C. A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus. Immunity. Published online March 8, 2016. DOI 10.1016/j.immuni.2016.02.012