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 toward HLA or blood groups (ABO) to allow better allocation and posttransplant longevity of organs. Antibodies originate from plasma cells (PCs), 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 PCs 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 PC 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 posttransplant antibody-directed therapy protocols are discussed.