Induction of MHC-mismatched mixed chimerism via anti-CD3/CD8–based conditioning corrects B-cell autoimmunity in NOD mice. Induction of MHC-mismatched mixed.

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Induction of MHC-mismatched mixed chimerism via anti-CD3/CD8–based conditioning corrects B-cell autoimmunity in NOD mice. Induction of MHC-mismatched mixed chimerism via anti-CD3/CD8–based conditioning corrects B-cell autoimmunity in NOD mice. NOD mice begin with intrinsic B-cell defects (upper panel, left) that give rise to expanded mature autoreactive B cells (lower panel, left). Early after HCT and before donor stem cell engraftment in anti-CD3/CD8–conditioned NOD recipients, the infused donor CD8+ T cells kill the pre-existing host-type autoreactive and nonautoreactive B cells in the lympho-hematopoietic tissues such as spleen (upper panel, right). Late after HCT, when de novo–developed B cells start entering the lymphoid tissues, the donor B cells outcompete host-type B cells for vital survival factors and induce host-type B-cell apoptosis (lower panel, right). This leads to a preferential depletion of host-type autoreactive B cells, since autoreactive B cells are more susceptible than nonautoreactive B cells. Jeremy J. Racine et al. Diabetes 2014;63:2051-2062 ©2014 by American Diabetes Association