title: Memory B cells form in aged mice despite impaired affinity maturation and germinal center kinetics.
abstract: We examined whether age alters the emergence of high-affinity germinal center B (GCB) cells and switched memory B cells (swBmem) during a primary immune response to a thymus-dependent antigen, using a novel flow cytometric assay to distinguish relative BCR affinity. In young mice, high-affinity B cells predominate in the GCB pool and comprise a smaller proportion of the nascent swBmem pool two weeks after immunization. In aged mice, we observe significant reductions of high-affinity clones among GCB cells, but not nascent swBmem cells. The defect in GC affinity maturation was not overcome by providing excess carrier-specific T cells from young mice, as these cells still displayed compromised effector TFH differentiation in the aged animals. Our results suggest that B cells in aged animals have a reduced ability to prompt effector TFH differentiation, leading to a compromised GC response that results in reduced generation of high-affinity GCB and plasma cells; despite normal production of early swBmem cells.
authors.affiliation: Dept. of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, United States. Electronic address: radzgoenka@gmail.com.
authors.forename: Radhika
authors.initials: R
authors.lastname: Goenka
authors.affiliation: Dept. of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, United States. Electronic address: jeanl@mail.med.upenn.edu.
authors.forename: Jean L
authors.initials: JL
authors.lastname: Scholz
authors.affiliation: Dept. of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, United States. Electronic address: smartin@mail.med.upenn.edu.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Naradikian
authors.affiliation: Dept. of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104-6082, United States. Electronic address: cancro@mail.med.upenn.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Cancro
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000637:transplantation; D002454:Cell Differentiation / Q000276:immunology; D018858:Germinal Center / Q000276:immunology*; D007156:Immunologic Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
keywords: Antibody affinity; Germinal center; Immune senescence; Memory B cell; T follicular helper