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Crosstalk between B and T cells in transplantation is increasingly recognized as being important in the alloimmune response. T cell activation of B cells occurs by a 3-stage pathway, culminating with costimulation signals. We review the distinct T cell subtypes required for B-cell activation and discuss the formation of the germinal center (GC) after transplantation, with particular reference to the repopulation of the GC after depletional induction, and the subsequent effect of immunosuppressive manipulation of T cell-B cell interactions. In addition, ectopic GCs are seen in transplantation, but their role is not fully understood. Therapeutic options to target T cell-B cell interactions are of considerable interest, both as immunosuppressive tools, and to aid in the further understanding of these important alloimmune mechanisms.

BACKGROUND: The last Banff 2013 report recognizes acute/active antibody-mediated rejection (ABMR) and C4d staining without evidence of rejection. The goal of our study was to analyze the incidence of C4d deposition after ABO-incompatible transplantation and assess outcomes in patients with ABMR, C4d staining without evidence of rejection (all acute Banff scores = 0), and C4d staining with tubulointerstitial inflammation (i > 0 with or without tubulitis). METHODS: Three-months 'For cause' or protocol biopsies in 50 ABO-incompatible patients were rescored and were correlated with clinical outcomes and antibody titres. RESULTS: Active/acute ABMR was found in 23 patients (46%), C4d staining without evidence of rejection in 7 patients (14%), C4d staining with tubulointerstitial inflammation in 6 patients (12%), tubulointerstitial inflammation in 6 patients (12%), and no evidence of rejection in 8 patients (16%). Patients with active/acute ABMR had a 3-month estimated glomerular filtration rate (median,: 43 mL/min) lower than patients with no evidence of rejection (median, 61 mL/min; P = 0.01). However, after 3 months, a progressively declining estimated glomerular filtration rate was observed more frequently in patients with C4d staining and tubulointerstitial inflammation when compared to patients with no evidence of rejection (100% vs 25%, P = 0.03). Finally, independently of C4d status, interstitial inflammation occurred more frequently in patients with a pretransplant ABO antibody titre higher than 16 and/or posttransplant ABO antibody increase. CONCLUSIONS: Whereas isolated C4d deposition and isolated interstitial inflammation appear to be benign lesions, C4d deposition in association with interstitial inflammation is the biopsy finding most strongly associated with the development of chronic graft dysfunction.