2011 - BSS 2011 Symposium


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Moderated Posters 1

5.20 - The fate of alloreactive B cells in transplantation tolerance: dysregulated inhibitory receptor expression of CD5, CD22,TIM-1 and MHC class II

Presenter: Jianjun, Chen, Chicago, United States
Authors: Jianjun Chen1, Soumi Mukherjee1, Jing Xu1, Tongmin Wang1, Yijin Li1, Roger Sciammas1, Anita Chong1

The fate of alloreactive B cells in transplantation tolerance: dysregulated inhibitory receptor expression of CD5, CD22,TIM-1 and MHC class II

Jianjun Chen1, Soumi Mukherjee1, Jing Xu1, Tongmin Wang1, Yijin Li1, Roger Sciammas1, Anita Chong1

1Section of Transplantation, Department of Surgery, The University of Chicago, Chicago, IL, USA

The role of B cells as a player in transplantation tolerance has recently come to the fore with the identification of a B cell gene expression “signature” associated with spontaneously tolerant kidney-transplanted individuals. To explore this phenomenon through the visualization of alloreactive B cells, we utilized an allo-specific B cell receptor (BCR) knock-in mouse model based on the MHC H2-kb-reactive 3-83 monoclonal antibody. 3-83 mice were transplanted with fully MHC-mismatched H2b cardiac allografts and were tolerized using a standard protocol of anti-CD154/DST. Tolerance was established normally despite the presence of a high frequency of alloreactive B cells. Strikingly, the tolerant B cell population was associated with two fates. In the blood and lymph nodes, the 3-83+ B cells had been deleted while, in the spleen, the 3-83+ B cells persisted, albeit at lower frequencies. In the spleen, balance of immature and mature compartments of the remnant 3-83+ B cells was altered such that a ratio of 1:1 mature to immature B cells was observed, rather than the 1:6 in naïve mice, respectively. Further, the immature 3-83+ population was not enriched for the recently described “T3” anergic population (CD93+, CD23+, IgMlo) suggesting that the regulation of these cells is occurring through alternative mechanisms. The phenotype of the remnant mature (CD93-) 3-83+ B cells was associated with dysregulated inhibitory receptor expression.  The 3-83+ B cells from tolerant mice were enriched for CD5hi (55.1 vs. 35.3%); TIM-1+ (9.2 vs. 1.5%), CD86(10.6% vs. 1.177%)as well as MHC Class II (MFI= 74488.8  vs 42603), and a reduction in CD22 expression (MFI=1143 vs. 1977) compared to 3.83+ cells from naive mice.  There was no difference in these markers for the non-alloreactive 3-83- B cells between tolerant and naive mice.  These observations suggest that differential inhibitory receptor expression underlies the fate of persisting alloreactive B cells during long-term maintenance of tolerance.

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