Figure 1.

T cell dependent B-cell differentiation. Following the receipt of signals provided by the microenvironment [e.g., Ag, CD4⁺ T (Tfh) cells, DC], naïve B cells undergo activation and can initially differentiate into either extrafollicular short-lived Ab-secreting plasma cells (secreting predominantly IgM), or can seed a germinal center (GC). Within GCs, B cells undergo somatic hypermutation of their Ig V region genes and only those B cells with the highest affinity are selected to then differentiate into long-lived memory B cells or plasma cells that are capable of secreting a variety of Ig isotypes, including the switched isotypes IgG, IgA, and IgE. The outcome of the GC reaction is heavily influenced by Tfh cells, especially those within the GC itself. These cells are not depicted on the figure but they contribute greatly at this stage of B-cell differentiation. Following re-encounter with the initiating Ag, memory B cells rapidly differentiate into plasma cells. The differentiation of naïve B cells to these distinct effector fates is controlled by the balanced expression and regulated function of various transcription factors, including (but not exclusively) PAX5, BCL-6, BLIMP-1, XBP-1, and IRF4.