Humoral immune response and B-cell functions including immunoglobulin class switch are downregulated in aged mice and humans.
Vaccinations are powerful tools for combating infections. Because of the age-related impairment in immune functions, the currently available vaccines are protecting only a small proportion of the elderly population. We, here, provide an overview of age-related changes in innate and adaptive immunity with particular emphasis to changes in antibody production with aging. We also summarize our results showing that the E2A-encoded transcription factor E47, which regulates many B cell functions including class switch recombination (CSR) and somatic hypermutation (SHM), is downregulated in splenic B cells from old mice. This leads to a reduction in the activation-induced cytidine deaminase (AID), which directly induces CSR and SHM, and, in turn, to reduced amounts of switched antibodies produced by splenic activated B cells. Our preliminary results in humans indicate similar reductions: we show herein that the expression of E2A and AID progressively decline with age. Our results provide a possible molecular basis for a decrease in the humoral immune response in aging mice and humans.
Frasca
Daniela
D
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, P.O. Box 016960 (R-138), Miami, FL 33101, USA.
Riley
Richard L
RL
Blomberg
Bonnie B
BB
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D016922:Cellular Senescence / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000502:physiology*; D051379:Mice