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Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging.


Maximus Peto’s Commentary

This looks remarkable: this group appears to have depleted B cells in older humans and then tested their response to hepatitis B vaccine. Some of these results from B cell depletion in mice and humans seem interesting and worth exploring further.


Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging.
Aging Cell. 2019 Aug;18(4):e12959.
Avivi I, Zisman-Rozen S, Naor S, Dai I, Benhamou D, Shahaf G, Tabibian-Keissar H, Rosenthal N, Rakovsky A, Hanna A, Shechter A, Peled E, Benyamini N, Dmitrukha E, Barshack I, Mehr R, Melamed D
DOI: 10.1111/acel.12959
PubMed publication date (edat): 5/6/2019

Abstract

Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B-cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B-cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B-cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B-cell compartments. B-cell depletion in old mice resulted in rejuvenated B-cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a “young”-like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B-cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in “dirty” environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a “young”-like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B-cell compartment in aging, through B-cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.

PMID: 31056853
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612643/

Maximus Peto

Max Peto is a longevity researcher and founder of Long Life Labs. A biochemist by training, he studies the biochemistry of aging and longevity and has worked with research organizations such as SENS Research Foundation, Methuselah Foundation, BioAge Labs, Life Extension Foundation, and Ichor Therapeutics. His work at Long Life Labs is focused on empowering people to understand and manage the most critical factors for better health and longer life.

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