From SAP-less T cells to helpless B cells and back: dynamic T-B cell interactions underlie germinal center development and function

Operation of the immune system critically depends on intercellular communication among multiple cell types, frequently in the form of physical cell-cell interactions. Germinal centers (GCs) are highly organized tissue microdomains in which high affinity, class-switched, antibody-producing cells and humoral immune memory are generated. Critical underlying cell-cell interaction events include at the minimum binary interactions between CD4(+) T-helper cells and antigen-presenting dendritic cells (DCs), which ensure proper T-cell activation and acquisition of effecter potentials, and those between T-helper cells and antigen-activated B cells whereby the latter cells receive helper signals (e.g. CD40L) important for their proliferation, survival, and differentiation. How these critical cellular interaction events are molecularly regulated and dynamically orchestrated to support GC formation and function is still a study in progress. Signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) has recently been defined as a pivotal molecule that controls cognate T-B interactions and GC formation. Detailed analysis of interaction and migration dynamics of SAP-deficient T cells has raised the interesting possibility that T cell:antigen-presenting cell interactions underlying GC development and function are regulated in a cell type- and spatiotemporal stage-specific manner. This has important implications for our understanding of synapse formation, helper signal delivery to B cells, follicular helper T-cell differentiation, and quality control of the GC reaction in general. A model of selective T-B interactions involving bi-directional feedback and feed-forward logic is proposed to underlie GC development and function.