Date Published: July , 2012
Publisher: Blackwell Publishing Inc
Author(s): S Heidt, J Hester, S Shankar, P J Friend, K J Wood.
In organ transplantation, the composition of the B-cell compartment is increasingly identified as an important determinant for graft outcome. Whereas naïve and transitional B cells have been associated with long-term allograft survival and operational tolerance, memory B cells have been linked to decreased allograft survival. Alemtuzumab induction therapy effectively depletes B cells, but is followed by rapid repopulation up to levels exceeding base line. The characteristics of the repopulating B cells are currently unknown. We studied the phenotypic and functional characteristics of B cells longitudinally in 19 kidney transplant recipients, before and at 6, 9 and 12 months after alemtuzumab induction therapy. A transient increase in transitional B cells and cells with phenotypic characteristics of regulatory B cells, as well as a long-term dominance in naïve B cells was found in alemtuzumab-treated kidney transplant recipients, which was not influenced by conversion from tacrolimus to sirolimus. At all time-points after treatment, B cells showed unaltered proliferative and IgM-producing capacity as compared to pretransplant samples, whereas the ability to produce IgG was inhibited long-term. In conclusion, induction therapy with alemtuzumab results in a long-term shift toward naïve B cells with altered phenotypic and functional characteristics.
Humoral immunity is increasingly recognized as an important component of the alloimmune response. It is clear that alloantibodies produced by B cells can cause (hyper)acute graft rejection and it has been postulated that production of donor specific alloantibodies after transplantation may be an important cause of late graft loss (1,2). Interestingly, and in contrast, novel data suggest that B cells may play an important role in allograft survival and the development of operational transplant tolerance (reviewed in Ref. 3).
Increasing evidence suggests that B cells may contribute to transplant tolerance, potentially resulting in successful long-term graft outcome. In this study, we have shown that after alemtuzumab induction, the repopulating B-cell compartment is altered compared to that pretransplant, comprising mainly naïve B cells that produce IgM upon activation, and that these remain the dominant cell type for at least 12 months after alemtuzumab therapy. Furthermore, we have shown that following alemtuzumab treatment there are dynamic changes in the repopulating B-cell pool with a transient increase in transitional B cells, including B cells with phenotypic characteristics of Breg.