Regulatory B Cells and Allergic Diseases

Abstract

B cells are generally considered to positively regulate immune responses by producing antigen-specific antibodies. B cells are classified into classical CD5- conventional B cells and CD5+ B1 cells. The latter produce multi-specific autoantibodies and are thought to be involved in autoimmune diseases. However, evidence supporting a B cell negative regulatory function has accumulated over the past 30 years. Multiple reports have suggested that absence, or loss, of regulatory B cells exacerbates symptoms of both allergic (including contact hypersensitivity and anaphylaxis) and autoimmune (such as experimental autoimmune encephalomyelitis, chronic colitis, and collagen-induced arthritis) diseases, and in lupus-like models of autoimmunity. Regulatory B cells are characterized by production of the negative regulatory cytokines, IL-10 and TGF-β. IL-10-producing B cells were the first regulatory B cells to be recognized and were termed 'B10' cells. IL-10-producing regulatory B cells are of the CD19+CD5+IgMhiIgDloCD1dhi type. Recently, a TGF-β-producing regulatory B cell subset, Br3, has been shown to be related to immune tolerance in food allergies. Moreover, forkhead box P3 (Foxp3)-expressing B cells have also been identified in humans and may act as regulatory B cells (Bregs). The functional image of regulatory B cells is similar to that of regulatory T cells. Because of the proliferative and apoptotic responses of Br1 and Br3 cells in immune tolerance in non-IgE-mediated food allergy, reciprocal roles and counter-regulatory mechanisms of Br1 and Br3 responses are also suspected. Additionally, different roles for regulatory B and T cells at different time points during initiation and progression of autoimmune disease are described.

A B-1a cell subset induces Foxp3− T cells with regulatory activity through an IL-10-independent pathway

“…17,19 With the ability to produce high levels of regulatory cytokines such as IL-10, B-1a cells are considered B cells with regulatory function. 33 We showed that B-1a cells were potent IL-10-producing cells at steady state when compared with the conventional B-2 subsets (Figure 4a). Moreover, B-1a cells interacted with CD4 1 T cells as APCs, leading to a larger amount of IL-10 production in in vitro cocultures (Figure 4b and c).…”

“…32 Among the diverse Treg populations, Tr1 cells specifically arise from naive precursors in the presence of IL-10. 33 Tr1 differentiation can be driven by immature or tolerogenic DCs through an IL-10-dependent mechanism or by self-APCpulsed antigens in the presence of IL-10. 17,19 With the ability to produce high levels of regulatory cytokines such as IL-10, B-1a cells are considered B cells with regulatory function.…”

Regulatory B Cells and Allergy: Uncovering the Link

“…Thus, the capacity of Breg cells to suppress allergic airway inflammation seems to depend on the expression of CD1d, particularly in mice, but also presents an IL-10-dependent mechanism [7,[19][20][21]. Studies performed by van der Vlugt [16,22] have shown that schistosomes induce regulatory responses in both human and mouse CD1d hi B cells and that they can restore allergic inflammation by production of IL-10.…”

“…In food-allergic patients, the inhibitory role of IL-10-producing CD5 + B cells has been described [19]. Interesting results showing the clinical relevance of B reg cells were recorded in studies on specific oral immunotherapy protocols in patients with cow's milk allergy (CMA) [36].…”

“…These cells play essential roles in the induction of tolerance to non-IgE-mediated food allergy in atopic dermatitis [19]. TGF-β-producing Breg cells (Br3) were characterized in the allergic response to cow's milk [37].…”