Restricted specificity of peripheral alloreactive memory B cells in HLA-sensitized patients awaiting a kidney transplant
Abstract
The contribution of memory B cells in alloreactive humoral
responses remains poorly understood. Here we tested
the presence of circulating alloreactive memory B cells in
69 patients with end-stage renal disease under renal
replacement therapy, using an in vitro memory B
cell–stimulation assay combined with identification of IgG
human leukocyte antigen (HLA) antibodies in culture
supernatant. HLA antibody–producing memory B cells were
evidenced only in patients carrying serum HLA antibodies
following multiple classical HLA-immunizing events. In
patients with a previous renal allograft, alloreactive memory
B cells could be detected ranging from 6 to 32 years (mean
13.2 years) after transplantation. HLA antibodies produced by
memory B cells were also detected in the corresponding sera
and showed a restricted reactivity, targeting only a few
epitopes shared by several HLA antigens. In contrast, serum
HLA antibodies, not associated with the detection of specific
memory B cells, showed a broader pattern of specificities.
Thus, expansion and survival of alloreactive memory B cells is
alloantigen driven, and their frequency is related to the
‘strength’ of HLA immunization.