Allergy Asthma Immunol Res.  2011 Jul;3(3):168-177. 10.4168/aair.2011.3.3.168.

Regulatory B Cells and Allergic Diseases

• Noh G
• Lee JH

• KMID: 1803322
• DOI: http://doi.org/10.4168/aair.2011.3.3.168

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-beta. 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(+)IgM(hi)IgD(lo)CD1d(hi) type. Recently, a TGF-beta-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.

Keyword

Regulatory B cell; allergy; IL-10; TGF-beta; CD5+ B; atopic dermatitis; asthma; food allergy; tolerance; counter-regulation

MeSH Terms

Antibodies
Asthma
Autoantibodies
Autoimmune Diseases
Autoimmunity
B-Lymphocytes
B-Lymphocytes, Regulatory
Colitis
Cytokines
Dermatitis, Atopic
Dermatitis, Contact
Encephalomyelitis, Autoimmune, Experimental
Food Hypersensitivity
Humans
Hypersensitivity
Immune Tolerance
Interleukin-10
T-Lymphocytes
T-Lymphocytes, Regulatory
Transforming Growth Factor beta
Antibodies
Autoantibodies
Cytokines
Interleukin-10
Transforming Growth Factor beta

Figure

• 

  Fig. 1 Regulatory B and T cells. Tr1, Th3, and regulatory T (Treg) cells produce IL-10 and/or TGF-β, and express Foxp3. B cells also produce IL-10, TGF-β, and Foxp3; these are termed Br1, Br3, and regulatory B cells (Breg). The B cell system thus seems to be a mirror image of the T cell system.

• 

  Fig. 2 Reciprocal roles of IL-10 from Br1 and TGF-β from Br3 cells on Br1 and Br3 cells. Br1 and Br3 cells belong to the CD5+ B cell subset. Growth of CD5+ B cells is stimulated by IL-10 in an autocrine manner, while TGF-β induces their apoptosis. IL-10 produced by Tr1 cells and TGF-β by Th3 cells have the same effects on CD5+ B cells.

• 

  Fig. 3 Proliferative and simultaneous apoptotic responses of Br1 and Br3 cells to casein in milk-tolerant subjects. IL-10-producing Br1 and TGF-β-producing Br3 cells proliferate while simultaneously showing apoptotic changes. IL-10 may stimulate proliferation of Br1 and Br3 cells, while TGF-β may induce their apoptosis.

• 

  Fig. 4 Reconstruction of Br1 and Br3 cell counter-regulatory mechanisms during induction of tolerance to allergen stimulation. IL-10 produced by Br1 cells mediates counter-regulatory effects through the IL-10/IL-27/IL-21 pathway. TGF-β produced by Br3 cells also induced apoptosis of both Br1 and Br3 cells. Moreover, activation-mediated apoptosis plays a role in counter-regulation of immune responses.

• 

  Fig. 5 Reciprocal roles of regulatory B and T cells. IL-10 from Br1 and Tr1 cells induces Tr1 and Treg cells. TGF-β produced by Br3 and Th3 cells induces Treg cells, which then act to suppress Br1 cells.

• 

  Fig. 6 Regulatory roles of regulatory B and T cells. Regulatory T and B cells function at different time points during initiation and progression of autoimmune diseases. Br1 and Br3 cells are decisive for tolerance induction in non-IgE-mediated food allergy related to atopic dermatitis. In contrast, there has been no report of the role of Tregs in the development of allergy or tolerance. The roles of regulatory T and B cells in non-IgE-mediated food allergy related to atopic dermatitis may thus be similar to those in autoimmune disease.

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