B Cell Regulation in Autoimmune Diseases

Abstract

Antibody-independent B cell effector functions play an important role in the development and suppression of the immune response. An extensive body of data on cytokine regulation of the immune response by B lymphocytes has been accumulated over the past fifteen years. In this review, we focused on the mechanisms of inflammatory response suppression by subpopulations of regulatory B cells in health and autoimmune pathologies.

Keywords: Breg, regulatory B cells; CD19+CD24(hi)CD38(hi); IL-10; IL-35; Multiple sclerosis; experimental autoimmune encephalomyelitis; rheumatoid arthritis; systemic lupus erythematosus.

Fig. 1

Mechanisms of regulatory B cell functioning and their impact on immune cells. Regulatory B cells produce anti-inflammatory cytokines that induce the formation of regulatory T cells and support invariant natural killers (iNKT), shown by black arrows. Breg-produced interleukins inhibit the differentiation of T follicular helpers, T helpers 1 and 17, inhibit the cytotoxic activity of T-lymphocytes (CD8⁺), and inhibit the production of pro-inflammatory cytokines by monocytes and dendritic cells (red arrows). Additionally, regulatory B cells reduce inflammation through direct cell contact, expression of B and T lymphocyte attenuators (BTLA), programmable death receptor ligands (PD-L1), production of IgM, IgG4, etc.

Fig. 2

Participation of regulatory B cells in the pathogenesis of multiple sclerosis. During the disease, Bregs can suppress the development of the autoimmune reaction, along with production of autoantibodies, autoantigen presentation, and activation of the T cell response. Various subpopulations of regulatory B cells with corresponding surface markers were identified in murine models and MS patients. In most cases, the immunosuppressive function of Breg is performed by the production of IL-10, IL-35, TGF-β, and direct cell-cell interactions

Fig. 3

Participation of regulatory B cells in the development of systemic lupus erythematosus. During the disease, B cells participate in the regulation of the autoimmune inflammation, along with the production of autoantibodies to nuclear autoantigens. Various subpopulations of regulatory B cells with corresponding surface markers were identified in murine models and patients with SLE, whose number increases with the course of the disease. An apparent protective role of Bregs was shown in animal models. In patients with SLE, the mechanism is not fully understood at the moment

Fig. 4

Participation of regulatory B cells in the development of rheumatoid arthritis. During the disease, B cells participate in the regulation of the autoimmune inflammation, along with the production of autoantibodies. Three main subpopulations of regulatory B cells were discovered in RA patients. CD19⁺CD24^hiCD38^hi demonstrated a suppression of the inflammatory response by inhibiting Th17 activity and reducing the level of IFN-γ and TNF-α in a IL-10-dependent manner. The mechanism and role of the CD19⁺CD5⁺CD1dhi and CD19⁺TGF-β⁺ subpopulations in the development of RA has not yet been clearly identified. An apparent protective role of IL-10 was shown in animal models. Participation of IL-35 and TGF-β is in question