Figure 1.

The B-cell response. B cells undergo clonal expansion and affinity maturation after encountering antigen and T-cell help or co-stimulatory signals, a process that generally occurs in germinal centres within secondary lymphoid organs.^12,13 Affinity maturation involves two processes, somatic hypermutation and clonal selection. Somatic hypermutation is a cytidine-deaminase-mediated process in which antibody CDRs are mutated ~1–2 times per cell division. Clonal selection involves competition of B cells for antigen and growth factors in germinal centres, resulting in B cells that express the highest-affinity antibodies being selected to expand and survive.^12,13 After multiple rounds of somatic hypermutation and clonal selection, antibody-expressing B cells produce antibodies with increased affinity for their target antigen.¹⁰ B cells that express high-affinity antibodies respond further to growth factors and other signals that induce differentiation into plasmablasts and memory B cells.^11,14,15 Plasmablasts transiently circulate in the blood and migrate to secondary lymphoid organs and tissues involved in the disease process, including tissues under autoimmune, infectious or malignant attack. Memory B cells circulate in the blood, and enable rapid recall responses upon re-exposure to their target antigen, whereas plasma cells localize primarily in the bone marrow and lamina propria, where they secrete antibodies. Abbreviation: CDRs, complementarity determining regions; FDC, follicular dendritic cell.