What does this research mean for the field?

B-cell receptor immunoglobulin heavy chain (BCR IGH) gene repertoire diversity decreases significantly after age 60, coinciding with increased low-level clonality driven by switched memory and age-associated B-cells. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate longitudinal alterations in the B-cell receptor immunoglobulin heavy chain (BCR IGH) repertoire and trace emergent low-level clonality during natural human aging.

September 3, 2026Immunity & AgeingOpen Access

Longitudinal analysis of the B-cell receptor repertoire across 30 years of ageing

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To evaluate longitudinal alterations in the B-cell receptor immunoglobulin heavy chain (BCR IGH) repertoire and trace emergent low-level clonality during natural human aging.
Analyzed 548 repeated blood samples collected at 5-year intervals over a 30-year follow-up from 98 participants aged 31–59 years at baseline within the Doetinchem Cohort study.
Sequenced BCR IGH gene repertoires and evaluated age-related impacts on repertoire diversity and clonality using linear mixed effects modeling.
Participants older than 60 years demonstrated heightened BCR IGH clonality alongside decreased repertoire diversity, which was significantly reduced in participants with a dominant clonotype ratio exceeding 10 (β = -0.57, p < 0.001).
Trends toward lower diversity were recorded in individuals aged 60–70 years (β = -0.19, p = 0.10) and those aged 70 years or older (β = -0.20, p = 0.13).
Repertoire diversity was primarily sustained by naïve and transitional B-cell subsets, whereas clonality was largely driven by switched memory and age-associated B-cells.

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Implication

Longitudinal cohort study reveals declining B-cell receptor diversity and emerging clonality in adults over age 60, highlighting progressive immune aging.

Cite This Study

Leenders et al. (2026) studied this question.

synapsesocial.com/papers/6a9934b4636c6408cfa7c6cd https://doi.org/10.1186/s12979-026-00596-2

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Implication

Longitudinal cohort study reveals declining B-cell receptor diversity and emerging clonality in adults over age 60, highlighting progressive immune aging.

Longitudinal analysis of the B-cell receptor repertoire across 30 years of ageing

Key Points

Discussion

Implication

Cite This Study

Longitudinal analysis of the B-cell receptor repertoire across 30 years of ageing

Key Points

Discussion

Implication

Cite This Study

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