High Expression of CXCR5 and ICOS identifies of follicular B helper T cells

T cell dependent immune responses rely on an intricate interplay of B cells, T cells, and dendritic cells within secondary lymphoid tissues. They typically lead to the formation of germinal centers (GC), where activated B cells differentiate into long-lived, high affinity antibody-secreting plasma cells. GC formation and the GC reaction critically depend on the presence of follicular B helper T (TFH) cells, a specialized subset of CD4 T cells providing B cell help. We were able to show that human TFHcells are characterized by high expression of CXCR5 and the co-stimulatory molecule ICOS, but independent of CD57 expression, a surrogate marker previously used to identify CD4 T cells with B helper T cell activity. CXCR5hiICOShi CD4 T cells are the most potent inducers of IgG secretion that also secrete large amounts of the B cell attracting chemokine CXCL13. CXCR5hiICOShi CD4 T cells differ from other CD4 T cell subsets in their stimulatory activity, proliferative capacity and susceptibility to apoptosis. Large-scale gene expression analysis revealed that TFH cells are only distantly related to central memory as well as effector memory CD4 T cells present in the periphery. CXCR5hiICOShi CD4 T cells appear to be terminally differentiated T helper cells that express a unique set of transcription factors related to the Notch signaling pathway. Still, the relationship to CXCR5+CD4 T cells present in peripheral blood remains obscure. Thus, we continue analyzing TFH cells to better understand their differentiation pathway and their role in chronic inflammatory and autoimmune diseases.