Understanding the Mechanisms of Immune System Aging: Immune System Cell Development and Antibody Repertoires
The incidence of infectious diseases, autoimmune syndromes, and various forms of cancer is elevated in older adults, and consequently, age-related changes in adaptive immunity have been studied extensively. These age-related changes include reduced antibody production after immunization or infection, reduced affinities of the antibodies produced, and the increased production of autoantibodies. To understand the increased susceptibility to disease with age, it is necessary to study the age-related changes in the immune system. Lymphocytes are small white blood cells that are predominantly responsible for the activities of the immune system. The two major classes of lymphocytes are B cells and T cells, both of which recognize specific antigen targets and are responsible for the learning and memory of the immune system. B cells are also responsible for antibody production. A shift in the phenotypes of these cells from naïve cells to memory lymphocytes is seen with advancing age and this shift could explain the reduced capacity of older adults to produce immune responses to antigens that they have not previously encountered. The mechanisms underlying these age-related changes in B-cell function have not yet been clarified. This chapter focuses on how the repertoire diversity, population dynamics, and functions of B cells alter during the aging process. These findings extend our understanding of age-related adaptive immunity and may in the future provide a basis for interventions that delay immunosenescence. Understanding the reasons for age-related changes in the mechanisms that control B-cell populations is critical if we are to develop technologies to overcome these defects.
KeywordsAged Mouse Autoimmune Syndrome Peripheral Lymphoid Organ Repertoire Diversity Lymphocyte Precursor
The work was supported in part by the Israel Science Foundation (grant number 270/09) and a grant from the BIU-Sheba joint research fund (to RM et al); a Human Frontiers Science Program Research Grant to RM and DDW; and grants from the Swedish MRC, the Magnus Bergvalls Foundation and the Karolinska Institutet (to FC). Gitit Lavy-Shahaf is supported by an ERAAGE FLARE postdoctoral fellowship, financed by the Israel ministry of health.
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