Introduction

A complete understanding of the role of antigen-specificity in the development of B cell mediated allograft tolerance has remained elusive. Previous work in our lab has demonstrated that regulatory B cells can be induced in vivo with treatment of anti-CD45RB, resulting in allograft tolerance. Furthermore, through adoptive transfer experiments, we have found that regulatory B cells from B6 animals tolerant to Balb/C islets fail to transfer tolerance to C3H islets, suggesting that antigen-recognition is required for the proper function of these regulatory B cells. To further understand the importance of antigen specificity in B cell mediated allograft tolerance, we have utilized BCR transgenic mice (OB-1) specific for ovalbumin to study the details of BCR antigen specificity for developing allograft tolerance.

Methods

T and B cells from WT and OB-1 mice were characterized using flow cytometry and MLR utilized OVA-specific transgenic CD4 T cells. Skin from OVA+ or third party mice (BM12) was transplanted onto WT, OB-1, or uMT mice, with or without anti-CD45RB treatment. For adoptive transfer experiments, B cells were isolated from WT and OB-1 mice tolerant to OVA+ skin grafts and transferred into uMT hosts.

Results

OB-1 and WT mice have similar distribution of B and T cells as well as Foxp3 T cells and B cell derived IL10 production, important for established role in Breg function. Similar to other models of allograft tolerance, our long-term studies now show survival of OVA+ skin grafts in WT and OB-1 mice treated with anti-CD45RB of >100 days, while rejection in the untreated animals is within 25 days (p<0.05). Adoptive transfer of B cells from tolerant mice also confers long-term tolerance to naïve hosts grafted with OVA+ skin. Experiments testing the survival of third party skin grafts after adoptive transfer of B cells from OVA+ skin tolerant hosts are ongoing.

Conclusion

We now have initial evidence that the OVA-specific BCR transgenic mouse B cells are capable to developing effective regulatory B cells producing long term allograft tolerance. These systems will allow for detailed investigation of the role of antigen recognition in the development and function of regulatory B cells for allograft tolerance development.

CITATION INFORMATION: Rickert C., Kimura S., Kojima L., Lee K., Aburawi M., Fontan F., Deng K., Yeh H., Markmann J. Achieving Allograft Tolerance through Antigen-Specific Regulatory B Cells Am J Transplant. 2017;17 (suppl 3).

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