Pre-transplant B cell depletion in NHP with Rituximab (IgG1 anti-CD20 mAb) combined with cyclosporin A has been shown to promote the survival of islets allografts. At the same time, B cell deficient uMT mice were shown to lack a donor-specific memory T cell response after transplantation. This suggests that B cell depletion could be used to prevent the development of T cell memory response in transplantation. Our group has studied the effect of anti-CD20 mediated B cell depletion on the memory T cell alloresponse in naïve and allosensitized mice. Wild-type and anti-OVA TCR transgenic mice were treated with an IgG2a anti-CD20 monoclonal antibody (5D2, Genentech), 5 days prior to skin transplantation, which depleted nearly all B cells in the peripheral blood and secondary lymphoid organs, but only reduced the B cell frequency in the bone marrow. Even though no effect was appreciated on the memory T cell direct alloresponse, the indirect response was significantly increased after skin transplantation of naïve mice. Furthermore, in allosensitized mice, anti-CD20 mAb treatment enhanced both direct and indirect reactivation of allospecific memory T cells and accelerated second set rejection of skin allografts. This suggests that the effect of anti-CD20 antibodies on alloimmunity and allograft rejection might vary upon the nature of the antibodies as well as the circumstances under which they are delivered.

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