Germinal Center Alloantibody Responses Mediate Progression of Chronic Allograft Injury

Germinal center alloantibody responses are mediated exclusively by indirect-pathway CD4 T follicular helper cells.

The durable alloantibody responses that develop in organ transplant patients indicate long-lived plasma cell output from T-dependent germinal centers (GCs), but which of the two pathways of CD4 T cell allorecognition is responsible for generating allospecific T follicular helper cells remains unclear. This was addressed by reconstituting T cell-deficient mice with monoclonal populations of TCR-...

Indirect-Pathway CD4 T Follicular Helper Are Mediated Exclusively by Germinal Center Alloantibody Responses

Model of Chronic Allograft Injury in Alloantibody Positive Renal Transplant Patients

Human Leukocyte Antigens (HLA) (donor-specific anti-HLA antibodies, DSA). Circulating DSA detected after implantation of the donor transplanted organ [de novo immunoglobulin G (IgG) DSA(dnDSA)] are now thought to be the major cause of allograft loss [14,15]. In the last 15 years, the body of knowledge on DSA has grown dramatically [14-34]. In the beginning, the research focused on the associati...

B cells mediate chronic allograft rejection independently of antibody production.

Chronic rejection is the primary cause of long-term failure of transplanted organs and is often viewed as an antibody-dependent process. Chronic rejection, however, is also observed in mice and humans with no detectable circulating alloantibodies, suggesting that antibody-independent pathways may also contribute to pathogenesis of transplant rejection. Here, we have provided direct evidence tha...

Computational Biology: Modeling Chronic Renal Allograft Injury

New approaches are needed to develop more effective interventions to prevent long-term rejection of organ allografts. Computational biology provides a powerful tool to assess the large amount of complex data that is generated in longitudinal studies in this area. This manuscript outlines how our two groups are using mathematical modeling to analyze predictors of graft loss using both clinical a...