Monitoring B cell subsets and alloreactivity in kidney transplantation

B cells are the precursors of antibody producing plasma cells that can give rise to the formation of donor-specific antibodies. However, recent data suggest that besides their role in antibody production, B cells participate in antibody-independent responses, potentially leading to allograft rejection or allograft tolerance. The presence of CD20(+) B cells in kidney graft biopsies has been shown during severe acute rejection episodes and during chronic rejection. Furthermore, operationally tolerant kidney transplant recipients showed a clear B cell dominated fingerprint of tolerance. Several techniques exist to study B cells on different levels. Numerous classification schemes allow for the distinction of many different B cell subsets using flow cytometry. Regardless, data on B cell subsets during stable graft function, rejection or tolerance remain scarce. To obtain a complete picture of the role of B cells during transplantation, antigen specific B cell assays may be required. Therefore, techniques have now been developed that allow for studying the specificity and frequency of HLA specific B cells. Here, we present an overview of the existent assays, panels and techniques intended to characterize peripheral B cells, and the currently available HLA specific B cell functional assays that may allow for monitoring the humoral alloimmune response in transplant recipients.