B cells and immunosenescence: a focus on IgG+IgD-CD27- (DN) B cells in aged humans.
Changes in the B-cell repertoire during aging include a shift in antibody specificities from foreign to autologous antigens associated with a decline in the activity of conventional B2 compared to B1 lymphocytes. The age-associated increase in B1 lymphocyte number and activity contribute to the increased serum concentration of autoantibodies and the B-cell clonal expansions that develop with age. Aging is also associated with a decreased diversity of the antibody response reflected in the preferential loss of IgG and high affinity antibodies following immunization with a foreign antigen. Many of these changes can be traced to an impaired capacity of T cells to support isotype switching and somatic mutation in the periphery and the generation of a diverse B-cell repertoire from bone marrow B-cell precursors.