The effect of desensitization protocols on human splenic B-cell populations in vivo.

Rituximab, intravenous immunoglobulin (IVIG) and rabbit antithymocyte globulin (rATG) all have been suggested to have an effect on antibody producing cells, however, supporting data are lacking. To assess the impact of these agents on splenic B-cell populations in vivo, we retrospectively examined 25 spleens removed from patients treated with these agents as part of desensitization protocols in either ABO incompatible or positive crossmatch living donor kidney transplantation. These were compared to control (CTL) spleens removed for trauma. CTLs and spleens removed at transplant after multiple pretransplant plasmaphereses (PP) plus low-dose IVIG showed similar large numbers of naïve B cells (CD20+ and CD79+), plasma cells (CD138+) and memory B cells (CD27+ cells). Adding rituximab to this PP/IVIG regimen reduced the number naïve B cells, but had no effect on memory or plasma cells. Combination treatment (PP/IVIG, rituximab and rATG) showed a trend toward the reduction of CD27+ cells, but again plasma cells were unchanged. We conclude that none of these protocols reduces splenic plasma cells in vivo. PP/low-dose IVIG does not alter splenic B cells, but the addition of rituximab decreases mature B cells. Memory B cells may be affected by combination therapy including rATG and requires further study.