In aged mice, low surrogate light chain promotes pro-B-cell apoptotic resistance, compromises the PreBCR checkpoint, and favors generation of autoreactive, phosphorylcholine-specific B cells

Aging Cell
Michelle RatliffRichard L Riley

Abstract

In aged mice, new B-cell development is diminished and the antibody repertoire becomes more autoreactive. Our studies suggest that (i) apoptosis contributes to reduced B lymphopoiesis in old age and preferentially eliminates those B-cell precursors with higher levels of the surrogate light chain (SLC) proteins (λ5/VpreB) and (ii) λ5(low) B-cell precursors generate new B cells which show increased reactivity to the self-antigen/bacterial antigen phosphorylcholine (PC). Pro-B cells in old bone marrow as well as pro-B cells from young adult λ5-deficient mice are resistant to cytokine-induced apoptosis (TNFα; TGFβ), indicating that low λ5 expression in pro-B cells is sufficient to cause increased survival. Transfer of TNFα-producing 'age-associated B cells' (ABC; CD21/35(-) CD23(-)) or follicular (FO) B cells from aged mice into RAG-2 KO recipients led to preferential loss of λ5(high) pro-B cells, but retention of λ5(low), apoptosis-resistant pro-B cells. In old mice, there is increased reactivity to PC in both immature bone marrow B cells and mature splenic FO B cells. In young mice, absence of λ5 expression led to a similar increase in PC reactivity among bone marrow and splenic B cells. We propose that in old age, increased apop...Continue Reading

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Citations

Jan 18, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa M Russell KnodePatricia J Gearhart
Mar 16, 2019·Frontiers in Immunology·Shiliang MaYi Hao
Dec 18, 2020·Frontiers in Aging Neuroscience·Season K Wyatt-Johnson, Randy R Brutkiewicz
Oct 11, 2017·Experimental Gerontology·Vincent HurezTyler J Curiel
Jun 7, 2020·Experimental Gerontology·Verena Labi, Emmanuel Derudder
Sep 26, 2019·Gerontology·Magdalena Hagen, Emmanuel Derudder

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Methods Mentioned

BETA
PCR
flow cytometry
FCS

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