title: Aging affects B-cell antigen receptor repertoire diversity in primary and secondary lymphoid tissues.
abstract: The elderly immune system is characterized by reduced responses to infections and vaccines, and an increase in the incidence of autoimmune diseases and cancer. Age-related deficits in the immune system may be caused by peripheral homeostatic pressures that limit bone marrow B-cell production or migration to the peripheral lymphoid tissues. Studies of peripheral blood B-cell receptor spectratypes have shown that those of the elderly are characterized by reduced diversity, which is correlated with poor health status. In the present study, we performed for the first time high-throughput sequencing of immunoglobulin genes from archived biopsy samples of primary and secondary lymphoid tissues in old (74 ± 7 years old, range 61-89) versus young (24 ± 5 years old, range 18-45) individuals, analyzed repertoire diversities and compared these to results in peripheral blood. We found reduced repertoire diversity in peripheral blood and lymph node repertoires from old people, while in the old spleen samples the diversity was larger than in the young. There were no differences in somatic hypermutation characteristics between age groups. These results support the hypothesis that age-related immune frailty stems from altered B-cell homeostasis leading to narrower memory B-cell repertoires, rather than changes in somatic hypermutation mechanisms.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.|Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Hilla
authors.initials: H
authors.lastname: Tabibian-Keissar
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Lena
authors.initials: L
authors.lastname: Hazanov
authors.affiliation: Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ginette
authors.initials: G
authors.lastname: Schiby
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Noemie
authors.initials: N
authors.lastname: Rosenthal
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Aviya
authors.initials: A
authors.lastname: Rakovsky
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Miri
authors.initials: M
authors.lastname: Michaeli
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Gitit Lavy
authors.initials: GL
authors.lastname: Shahaf
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Yishai
authors.initials: Y
authors.lastname: Pickman
authors.affiliation: Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.
authors.forename: Kinneret
authors.initials: K
authors.lastname: Rosenblatt
authors.affiliation: Department of Immunology, Technion Faculty of Medicine, Haifa, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
authors.affiliation: Division of Immunology, Infection, and Inflammatory Diseases, King's College London, Faculty of Life Sciences & Medicine, London, United Kingdom.
authors.forename: Deborah
authors.initials: D
authors.lastname: Dunn-Walters
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel.
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
authors.affiliation: Department of Pathology, Sheba Medical Center, Ramat Gan, Israel.|Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000276:immunology*; D000916:Antibody Diversity / Q000502:physiology*; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D027041:Somatic Hypermutation, Immunoglobulin; D055815:Young Adult
chemical_list: D011947:Receptors, Antigen, B-Cell
keywords: Aging; B cells; Bone marrow; Immunoglobulin repertoire; Secondary lymphoid tissues