Regulatory B cell

One of the main mechanisms is the production of anti-inflammatory cytokines such as interleukin 10 (IL-10), IL-35, or transforming growth factor beta (TGF-β).

Another known mechanism is the production of cytotoxic Granzyme B. Bregs also express various inhibitory surface markers such as programmed death-ligand 1 (PD-L1), CD39, CD73, and aryl hydrocarbon receptor.

The regulatory effects of Bregs were described in various models of inflammation, autoimmune diseases, transplantation reactions, and in anti-tumor immunity.

[6] Then a role of Bregs was found in many mouse models of autoimmune diseases as rheumatoid arthritis[7] or systemic lupus erythematosus (SLE).

Human and murine Bregs can be further separated into many subsets due to their different mechanism of action and distinct expression of key surface markers (table below).

[24] Likewise, regulatory B cell subsets have also been demonstrated to inhibit Th1 responses through IL-10 production during chronic infectious diseases such as visceral leishmaniasis.

[11] Another mechanism of Breg suppression involves surface molecules such as FasL, which induces T cell death,[27] or PD-1 and PD-L1.

After the response to antigen or different stimuli such as lipopolysaccharide (LPS) pro- and anti-inflammatory cytokines TNFα, IL-1β, IL-10 and IL-6 are produced.

Additionally, cytokine IL-21 together with CD40 ligand and/or TLR9 signals has been shown to induce B10 generation and the emergence of IL-10 producing plasmablasts during inflammatory processes.

[3] Bregs are studied in several human autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis, SLE, type 1 diabetes, or Sjögren's syndrome.

It has been reported that an approved medication for MS treatment Glatiramer acetate increases Breg frequencies and enhances their function.

In type 1 diabetes (T1D), the evidence suggests that IL-10–producing Bregs are numerically and functionally defective in patients compared to healthy donors.

[31] Moreover, increased levels of Bregs were detected in the peripheral blood and bone marrow of patients with acute myeloid leukemia.

[30] It has been reported that patients undergoing kidney transplantation who were subjected to B-cell depletion therapy showed a higher incidence of graft rejection.

Murine models of allotransplantation showed that Bregs increased the duration of allograft survival and controlled Th17, Tfh, and follicular regulatory T-cell differentiation.