Effects of B cell depletion on T cell allogeneic immune responses: a strategy to reduce allogeneic sensitization.

BACKGROUND: B cell depletion has been employed to treat antibody-mediated organ transplantation rejection, although the effects on cellular immune responses have not been extensively investigated.
METHODS: A model of B cell depletion used SCID/beige mice reconstituted with BALB/c splenocytes either depleted of B cells (BD) or not (BN). BD and B/N mice received C57BL/6 skin grafts and were sacrificed after 6 weeks (BD-S6 and BN-S6).
RESULTS: Recall proliferative responses of BD-S6 splenocytes to C57BL/6 were significantly reduced compared to BN-S6, and central memory T cells' proportions (CD4(+)CD44(+)CD62L(+) or CD8(+)CD44(+)CD62L(+)) were significantly decreased in BD-S6 spleens. Recall IFN-gamma production by BD-S6 splenocytes was significantly reduced compared to BN-S6 splenocytes (p=0.0028). Survival times of C57BL/6 heart grafts were significantly longer in SCID/beige mice reconstituted with BD-S6 splenocytes (8.5+/-1.1 days) than for SCID/beige reconstituted with BN-S6 splenocytes (6.0+/-1.1 days; p=0.0006). Under cyclosporine therapy, C57BL/6 heart survival was significantly longer for SCID/beige reconstituted with BD-S6 splenocytes (17.5+/-6.4 days) than those reconstituted with BN-S6 splenocytes (6.2+/-1.5 days; p<0.0001).
CONCLUSION: B cell depletion during allogeneic sensitization decreased memory T cells and recalls IFN-gamma production and reduced second-set allograft rejection.