Regulatory B cells in respiratory health and diseases

Abstract

B cells are critical mediators of humoral immune responses in the airways through antibody production, antigen presentation, and cytokine secretion. In addition, a subset of B cells, known as regulatory B cells (Bregs), exhibit immunosuppressive functions via diverse regulatory mechanisms. Bregs modulate immune responses via the secretion of IL-10, IL-35, and tumor growth factor-β (TGF-β), and by direct cell contact. The balance between effector and regulatory B cell functions is critical in the maintenance of immune homeostasis. The importance of Bregs in airway immune responses is emphasized by the different respiratory disorders associated with abnormalities in Breg numbers and function. In this review, we summarize the role of immunosuppressive Bregs in airway inflammatory diseases and highlight the importance of this subset in the maintenance of respiratory health. We propose that improved understanding of signals in the lung microenvironment that drive Breg differentiation can provide novel therapeutic avenues for improved management of respiratory diseases.

Keywords: B cells; IL-10; airway inflammation; immune regulation; infection; lung.

FIGURE 1

Mechanisms of immune suppression by Bregs. Human Bregs suppress Th1 and Th17 responses, and inhibit cytotoxic activity by CD8⁺ T cells. They also induce the differentiation of CD4⁺T cells into FoxP3⁺ Tregs and IL‐10⁺ T regulatory‐1 (Tr1) cells. In addition to modulating T cell responses, they suppress TNFα production by monocytes, IFN‐α production by plasmacytoid dendritic cells (pDCs) and IL‐12‐producing DCs. Breg‐mediated suppression of the immune response is achieved predominantly via the production of IL‐10, and to an extent by TGF‐β and IL‐35 production. Further, immune suppression by Bregs can be mediated via co‐stimulatory interactions with T cells, invariant natural killer T (iNKT) cells and DCs. Bregs support iNKT cell homeostasis by presenting lipid antigens via CD1d to the invariant T cell receptor (iTCR)