ADAPTIVE IMMUNE RESPONSES Differentiation of Effector T Cells and B Cells T-cell differentiation proceeds in the same zones of the secondary organs as T-cell clonal expansion. Naïve T cells and recent thymic emigrants (RTE) involved in adaptive immune responses become activated T cells that differentiate into effector CD4+ and CD8+ T cells and memory CD4+ and CD8+ T cells. Effector T cells appear to be the final stage of T-cell differentiation. During maturation, T cells progressively change their phenotype but not morphological shape. They enhance the expression of some cell adhesion molecules, LFA-1 and CD2, lose L-selectin (CD62L-), some other important molecules (CD27- and CD28-), and begin to display CCR5, CXCR3, and HLA-DR. By 10th day of a typical infectious case, they all become effector and memory T cells with the same affinity of the TCR for the causative antigen. CD8+T cells turn into cytotoxic T cells, whereas CD4+T cells continue to differentiate into both subsets of helper T cells and inflammatory T cells. B-cell differentiation starts out in the same follicles of the secondary organs as B-cell clonal expansion proceeds, but subsequently, it partially relocates to the bone marrow and somewhat to the MALT. As opposed to T-cell differentiation, for B-cell maturation specific morphological changes are characteristic. In the beginning, B cells develop into immunoblasts, and next, they become lymphoplasmacytoid cells. Plasma cells are the terminal stage of B-cell differentiation. The plasma cells, effector cells of B-cell-mediated responses, contribute to antibody synthesis. Within 1-2 days in a typical infectious case, IgM synthesis occurs. However, due to the somatic hypermutations by the 5th-7th days of the case, the high-affinity B cells are generated in the plasma cells, which can produce IgG. Plasma cells produce enormous amounts of antibodies, about 2000 molecules per second. Antibody switching is dependent on cytokines and costimulatory molecules. In addition, CD40L-CD40 interaction is strictly required for both antibody switching and the formation of memory B cells. ©V.V.Klimov