PhDB cells contribute to chronic allograft deterioration, negatively impacting graft
survival, and curtailing the lifespan of a resource already in short supply. Given this,
identifying alloreactive B cells could generate an important target in the battle
against rejection. This study described an IgG-detecting ELISPOT used to determine
if the risk of developing antibody-mediated rejection (AMR) could be predicted pretransplantation
by in vitro analysis of allospecific B cells. This method failed to
discriminate accurately B-cell responses to donor antigen. An alternative approach
used was to detect peripheral HLA-specific B cells. Circulating HLA–A*0201 and –
DQB1*0301 B cells were identified at higher frequency in sensitised patients, and
this correlated with the level of serum alloantibody. Expression of HLA-DQB1*0301
B cells were at a higher frequency than HLA-A*0201 B cells in those with serum de
novo donor-specific antibody (dnDSA). Next, levels of B-cell activating factor (BAFF)
were investigated. Excess BAFF has been related to rejection and the development
of DSA. Here elevated serum BAFF, low BAFF-receptor and DSA were all associated
with deteriorating graft function. In addition intrarenal CD19+ cells, BAFF and BAFFreceptor
identified with acute AMR.
In contrast to a pathogenic role of B cells, a small population may be protective. The
presence of regulatory B cells, defined by IL-10 production were higher in those
with stable graft function, and identified with naïve B cells rather than memory B
cells when compared to those with deteriorating grafts. The CD19+CD24highCD38high
subset was also elevated in stable patients, and the ability to supress T-cell
activation and secretion of the Th1 cell pro-inflammatory cytokine, IFN-γ was
altered as a function of allograft stability.
These data demonstrated characteristics within the B-cell compartment associated
with stable graft function. The ability to monitor these cells may have clinical
implications for predicating the risk of rejection, to dictate immunosuppressive
therapy and promote allograft survival.Central London Research Ethics Committee (REC1: 07/H0707/10)
Funding: NHS Blood and Transplant (UKT06-4
