B-lymphocyte homeostasis and BLyS-directed immunotherapy in transplantation.

Transplantation Reviews
Ronald F ParsonsHooman Noorchashm

Abstract

Current strategies for immunotherapy after transplantation are primarily T-lymphocyte directed and effectively abrogate acute rejection. However, the reality of chronic allograft rejection attests to the fact that transplantation tolerance remains an elusive goal. Donor-specific antibodies are considered the primary cause of chronic rejection. When naive, alloreactive B-cells encounter alloantigen and are activated, a resilient "sensitized" state, characterized by the presence of high-affinity antibody, is established. Here, we will delineate findings that support transient B-lymphocyte depletion therapy at the time of transplantation to preempt sensitization by eliminating alloreactive specificities from the recipient B-cell pool (ie, "repertoire remodeling"). Recent advances in our understanding of B-lymphocyte homeostasis provide novel targets for immunomodulation in transplantation. Specifically, the tumor necrosis factor-related cytokine BLyS is the dominant survival factor for "tolerance-susceptible" transitional and "preimmune" mature follicular B-cells. The transitional phenotype is the intermediate through which all newly formed B-cells pass before maturing into the follicular subset, which is responsible for mounting ...Continue Reading

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Citations

Feb 15, 2012·Immunology Letters·Jean L Scholz, Michael P Cancro
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Jan 30, 2015·Tissue Antigens·G D Banham, M R Clatworthy
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Aug 6, 2013·Transplant International : Official Journal of the European Society for Organ Transplantation·Menna R Clatworthy
Jan 21, 2012·Transplantation·Ronald F ParsonsHooman Noorchashm
Jun 18, 2019·Clinical Transplantation·Kevin S Shah, Jignesh Patel
Sep 24, 2013·Transplantation·Mark D StegallPatrick G Dean
Jun 17, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·E Steve WoodleDavid Hildeman

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