Universität zu Köln

Bradshaw, William John, Poeschla, Michael, Placzek, Aleksandra, Kean, Samuel and Valenzano, Dario Riccardo ORCID: 0000-0002-8761-8289 (2022). Extensive age-dependent loss of antibody diversity in naturally short-lived turquoise killifish. eLife, 11. CAMBRIDGE: eLIFE SCIENCES PUBL LTD. ISSN 2050-084X

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Abstract

Aging individuals exhibit a pervasive decline in adaptive immune function, with important implications for health and lifespan. Previous studies have found a pervasive loss of immune-repertoire diversity in human peripheral blood during aging; however, little is known about repertoire aging in other immune compartments, or in species other than humans. Here, we perform the first study of immune-repertoire aging in an emerging model of vertebrate aging, the African turquoise killifish (Nothobranchius furzeri). Despite their extremely short lifespans, these killifish exhibit complex and individualized heavy-chain repertoires, with a generative process capable of producing millions of distinct productive sequences. Whole-body killifish repertoires decline rapidly in within-individual diversity with age, while between-individual variability increases. Large, expanded B-cell clones exhibit far greater diversity loss with age than small clones, suggesting important differences in how age affects different B-cell populations. The immune repertoires of isolated intestinal samples exhibit especially dramatic age-related diversity loss, related to an elevated prevalence of expanded clones. Lower intestinal repertoire diversity was also associated with transcriptomic signatures of reduced B-cell activity, supporting a functional role for diversity changes in killifish immunosenescence. Our results highlight important differences in systemic vs. organ-specific aging dynamics in the adaptive immune system.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bradshaw, William John UNSPECIFIED UNSPECIFIED UNSPECIFIED Poeschla, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Placzek, Aleksandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Kean, Samuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Valenzano, Dario Riccardo UNSPECIFIED orcid.org/0000-0002-8761-8289 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-668078
DOI:	10.7554/eLife.65117
Journal or Publication Title:	eLife
Volume:	11
Date:	2022
Publisher:	eLIFE SCIENCES PUBL LTD
Place of Publication:	CAMBRIDGE
ISSN:	2050-084X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MECHANISMS; INSIGHTS; PACKAGE; TOOLKIT; FISHES; GENOME; MODEL Multiple languages Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/66807