Abstract |
In young adult BALB/c mice, antibodies to phosphorylcholine (PC) bearing the T15 (TEPC 15) idiotype confer protection against pneumococcal infections. In old age, even though PC reactive B cells are often increased, the proportion of T15+ antibodies declines. We hypothesize that limited surrogate light chain (SLC) and compromise of the pre-B cell receptor checkpoint in old mice contribute to both reduced new B cell generation and changes in the anti-PC antibodies seen in old age. In old mice: 1) early pre-B cell loss is most pronounced at the preBCR checkpoint; however, the reduced pool of early pre-B cells continues to proliferate consistent with preBCR signaling; 2) increased PC reactivity is seen in bone marrow immature B cells; 3) deficient SLC promotes increased B cell PC reactivity and diminished T15 idiotype expression; and 4) as pre-B cell losses and reduced SLC become progressively more severe, increased T15 negative PC reactive B cells occur. These results associate a reduction in pre-B cells, imposed at the preBCR checkpoint, with increased reactivity to PC, but more limited expression of the protective T15 idiotype among PC reactive antibodies in old age.
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Authors | Kelly Khomtchouk, Sarah Alter, Michelle Ratliff, Bonnie B Blomberg, Richard L Riley |
Journal | Mechanisms of ageing and development
(Mech Ageing Dev)
Vol. 162
Pg. 53-62
(03 2017)
ISSN: 1872-6216 [Electronic] Ireland |
PMID | 27876385
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Autoantibodies
- Immunoglobulin Light Chains
- Receptors, Antigen, B-Cell
- Phosphorylcholine
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Topics |
- Aging
(immunology, pathology)
- Animals
- Autoantibodies
(immunology)
- Bone Marrow Cells
(immunology, pathology)
- Immunoglobulin Light Chains
(immunology)
- Mice
- Mice, Inbred BALB C
- Phosphorylcholine
(immunology)
- Precursor Cells, B-Lymphoid
(immunology, pathology)
- Receptors, Antigen, B-Cell
(immunology)
- Signal Transduction
(immunology)
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