Balancing enough immunosuppression to prevent allograft rejection and yet maintaining an intact immune system to respond to vaccinations, eliminate invading pathogens or cancer cells is an ongoing challenge to transplant physicians. Antibody mediated allograft rejection remains problematic in kidney transplantation and is the most common cause of graft loss despite current immunosuppressive therapies. The goal of immunosuppressive therapies is to prevent graft rejection; however, they prevent optimal vaccine responses as well. At the center of acute and chronic antibody mediated rejection and vaccine responses is the B lymphocyte. This review will highlight the role of B cells in alloimmune responses including the dependency on T cells for antibody production. We will discuss the need to improve vaccination rates in transplant recipients and present data on B cell populations and SARS-CoV-2 vaccine response rates in pediatric kidney transplant recipients.