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Breg Essay

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Regulatory B cells (Breg) are also termed “suppressive” cells due to their role in truncating the immune response by producing IL-10 60. They secrete transforming growth factor β (TGF-β) which induces apoptosis of CD4+ 61 and anergy in CD8+ effector T cells 62. Breg manipulation in mouse models has given insight to the role of Bregs and B cells in rejection; however, it has not yet been tested as a therapy for renal transplant. The genetic modification of mice to deplete Breg results in the development of chronic inflammation, indicating that induction of Breg can be a potential therapeutic modality in immune-mediated inflammatory conditions 63. Deletion of IL-10-producing genes from Bregs in mice is also associated with increasing …show more content…

This observation suggests that the ratio between IL-10 and TNF-α may correlate with the state of tolerance. A study conducted by Cherukuri et al. concluded that the IL-10/TNF-α ratio in transitional B cells (TrB) from recipients with chronic rejection was low compared with those with stable graft function 77. These biomarkers could be used to predict early graft rejection, as well as the ability to minimize immunosuppression and may guide future research in order to increase the rate of tolerance.
The role of Mesenchymal Stromal Cells (MSCs) in Transplantation
The interaction between MSCs, DCs, and natural killer (NK) cells is critical for each of their immunomodulatory functions. MSCs halt the antigen presenting potential of mature DCs by down regulating cell-surface expression of MHC class II molecules, CD11c, CD83, co-stimulatory molecules, and cytokines including interleukin-12, a mechanism which plays an indirect role in cellular anergy 78. MSCs decrease the pro-inflammatory potential of DCs by inhibiting their production of tumor-necrosis factor, and stimulating plasmacytoid DCs (pDCs) to produce the immunoregulatory cytokine IL-10 79. In addition, MSCs increase Tregs through secretion of pGE2, IL-10 (by pDCs), and TGF-β 80. In combination, these signals have the potential to enhance tolerance. NK cells oppose the effects of MSCs and the mutual interaction between MSCs and NK cells leads to a delicate balance of

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