title: B cells, E2A, and aging.
abstract: Both mouse and human exhibit deficiencies in humoral immunity during 'old age'. While alterations in phenotype and function have been well documented, the molecular mechanisms that result in immune senescence remain undefined. B lymphopoiesis is suppressed in senescent mice, which may result from deficits at the pre-B-cell stage or earlier (e.g. pro-B cells). This deficit contrasts with the maintenance of the normal number of total peripheral B lymphocytes in senescent mice. However, mature peripheral B cells in aged mice can exhibit reduced efficiencies of both immunoglobulin isotype switching and somatic hypermutation. The basic helix-loop-helix transcription factor E2A is crucial at several stages of B-lymphocyte differentiation, including the development of pro-B and pre-B cells within the bone marrow and in isotype switch and somatic hypermutation among peripheral B cells. Therefore, we have focused on the regulation of E2A expression and function during both B lymphopoiesis and isotype class switching in senescent mice. These studies show that E2A expression is normally under complex control at both post-transcriptional and post-translational levels. Alterations in E2A expression at both the B-cell precursor and mature B-cell developmental stages are hypothesized to contribute to defects in humoral immunity during senescence.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, FL 33101, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Riley
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Blomberg
authors.forename: Daniela
authors.initials: D
authors.lastname: Frasca
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D014157:Transcription Factors