Memory B-cells and Long-Lived Plasma Cells

The importance of B-cell and antibody-mediated immune response in the acute and long-term persistence of transplanted solid organs has become increasingly evident in recent years. A variety of therapeutic innovations target antibodies directed towards human leucocyte antigens (HLA) or blood groups (ABO) in order to allow better allocation and post-transplant longevity of organs. Antibodies originate from plasma cells, which are terminally differentiated B-cells. Long-term production and persistence of these antibodies is partly due to fast reactivation of previously generated memory B-cells; however, there is increasing evidence that some differentiated plasma cells can persist independently in the bone marrow for years or even decades, producing specific antibodies or even experiencing regeneration without proliferation without need to be replaced by newly differentiating B-cells. This review outlines the currently presumed pathways of differentiation, antibody and memory generation on both B-cell and plasma cell levels. On this background, current therapeutic concepts for antibody reduction before and after solid organ transplantation are considered, to better understand their mechanisms, possible synergisms and specific risks. Specific differences in regards to ABO versus HLA antibodies as well as practical relevance for generation of desensitization and post-transplant antibody-directed therapy protocols are discussed. LI and SU participated in review of the literature and writing of the paper. Corresponding author: Simon Urschel, MD , Associate Professor of Pediatrics and Immunology, Director Pediatric Cardiac Transplantation , University of Alberta / Stollery Children's Hospital , 4C2.24, Walter McKenzie Center , 8440 - 112 Street , Edmonton, AB, T6G 2B7 , Phone: +1 (780) 407 8361, Fax: +1 (780) 407 3954, Email: urschel@ualberta.ca Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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