FIGURE 23-37 Collaboration between T and B cells is required to initiate the production of antibodies. Left: Activation of T cells by means of antigen-loaded dendritic cells (DCs). Right: Antigen acquisition by and subsequent activation of B cells. Step 1: Professional antigen-presenting cells (dendritic cells, B cells) acquire antigen. Step 2: Professional APCs internalize and process antigen. T-cell activation occurs when dendritic cells present antigen to T cells. Step 3a: Activated T cells engage antigen-experienced B cells through peptide-MHC complexes displayed on the surface of the B cell. Step 3b: T cells that are persistently activated initiate expression of the CD40 ligand (CD40L), a prerequisite for B cells becoming fully activated and turning on the enzymatic machinery (AID) to initiate class-switch recombination and somatic hypermutation. Step 4a: A B cell that receives the appropriate instructions from CD4 helper T cells becomes an IgM-secreting plasma cell. Step 4b: A B cell that receives signals from activated CD4 helper T cells in the form of CD40–CD40L interactions and the appropriate cytokines can switch to other immunoglobulin isotypes and engage in somatic hypermutation.