Humoral immunity requires interaction between specialized populations of B cells and CD4⁺ T cells, called follicular helper T cells (T_FH cells), in the germinal center (GC) to produce memory B cells and long-lived plasma cells. Molecular crosstalk between GC B cells and T_FH cells influences the survival, proliferation and differentiation of each cell type. This pairing of GC B cells and T_FH cells also occurs at the transcriptional level as the Bcl-6–IRF4–Blimp-1 axis, which is crucial for B cell differentiation, is also essential for the T_FH cell identity. Less is known about the memory B cells that arise from the GC pool, as they seem to be distinctly 'programmed' on the basis of their antigen receptor affinity to enter the long-lived memory pool.