Role of regulatory B cells in immune tolerance to allergens and beyond

详细信息    查看全文

• 作者：Willem van de Veen ; PhD^a ; ^b ; Barbara Stanic ; PhD^a ; ^c ; Oliver F. Wirz ; MSc^a ; Kirstin Jansen ; MSc^a ; Anna Globinska ; MSc^a ; ^d ; M&uuml ; beccel Akdis ; PhD^a ; ^{akdism@siaf.uzh.ch" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Regulatory B cells ; IL-10 ; IL-35 ; TGF-β ; IgG4 ; tolerance ; allergen ; autoimmunity ; suppression ; BR1 ; B10
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：138
• 期：3
• 页码：654-665
• 全文大小：851 K

文摘

Immune tolerance to both self-antigens and innocuous non–self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion. However, IL-35 and TGF-β have also been associated with B cell–mediated immunosuppression. Several types of murine and human Breg cells have been described, such as mouse CD5⁺CD1d^hi B10 cells, CD21^hiCD23^hiCD24^hi transitional stage 2–like B cells, and CD138⁺ plasma cells and plasmablasts. Human Breg cell types include CD27⁺CD24^high B10 cells, CD24^hiCD38^hi immature transitional B cells, and CD73⁻CD25⁺CD71⁺ B_R1 cells and a subset of plasma cells. Support for the in vivo existence of allergen-specific human Breg cells comes from direct detection of their increase during the course of allergen-specific immunotherapy, as well as their increased expression in nonallergic but high-dose allergen–exposed beekeepers. Human B_R1 cells selectively upregulate IgG₄ antibodies on differentiation to plasma cells. This suggests an additional immune regulatory role because of the noninflammatory and blocking antibody function of IgG₄. Taken together, Breg cells appear to be involved in mediating allergen tolerance, but many open questions remain to be answered.