FIGURE 2.

T-B cell interactions and signals. The initial B cell activation signal is provided by cognate BCR-alloantigen interaction and requires the CD19, CD21, CD81 complex for an optimal signaling. Cognate Tfh cells provide costimulation after presentation of antigenic peptides in MHC class II by the B cells in the GC. T-B interactions, especially ICOS-ICOSL, CD40-CD40L, and CD28-B7 interactions, are central to this process. Members of the SLAM (Signaling lymphocytic activation molecule) family of receptors, particularly CD84, are also important for stable T-B cell interactions, which also contribute to Tfh cell differentiation through SAP (SLAM associated protein)-mediated signaling. Cytokines, IL-6 and IL-21 contribute to Tfh cell differentiation via upregulation of BCL-6. The crosstalk between T and B cells in the GC is bidirectional mediated by ligand-receptor interactions, soluble mediators (cytokines). Biologics targeting these signals can modulate posttransplant humoral response.