| First Author | Ratliff M | Year | 2015 |
| Journal | Aging Cell | Volume | 14 |
| Issue | 3 | Pages | 382-90 |
| PubMed ID | 25727904 | Mgi Jnum | J:222120 |
| Mgi Id | MGI:5643992 | Doi | 10.1111/acel.12302 |
| Citation | Ratliff M, et al. (2015) 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 14(3):382-90 |
| abstractText | 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 (lambda5/VpreB) and (ii) lambda5(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 lambda5-deficient mice are resistant to cytokine-induced apoptosis (TNFalpha; TGFbeta), indicating that low lambda5 expression in pro-B cells is sufficient to cause increased survival. Transfer of TNFalpha-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 lambda5(high) pro-B cells, but retention of lambda5(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 lambda5 expression led to a similar increase in PC reactivity among bone marrow and splenic B cells. We propose that in old age, increased apoptosis, mediated in part by TNFalpha-producing B cells, results in preferential loss of SLC(high) pro-B cells within the bone marrow. Further B-cell development then occurs via an 'SLC(low)' pathway that not only impairs B-cell generation, but promotes autoreactivity within the naive antibody repertoires in the bone marrow and periphery. |
