In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is associated with increased B cell reactivity to phosphorylcholine, but reduced T15 idiotype dominance

Kelly Khomtchouk, Sarah Alter, Michelle Ratliff, Bonnie B Blomberg, Richard L Riley

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)53-62
Number of pages10
JournalMechanisms of Ageing and Development
Volume162
DOIs
StatePublished - Mar 1 2017

Fingerprint

Surrogate Immunoglobulin Light Chains
B-Lymphoid Precursor Cells
Phosphorylcholine
Bone Marrow Cells
B-Lymphocytes
Antibodies
Pre-B Cell Receptors
Pneumococcal Infections
Young Adult
Anti-Idiotypic Antibodies
Bone Marrow

Keywords

  • Aging
  • Immature B cells
  • Phosphorylcholine
  • Pre-B cell receptor
  • Surrogate light chain
  • T15 idiotype

ASJC Scopus subject areas

  • Aging
  • Developmental Biology

Cite this

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title = "In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is associated with increased B cell reactivity to phosphorylcholine, but reduced T15 idiotype dominance",
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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T1 - In old BALB/c mice, bone marrow pre-B cell and surrogate light chain reduction is associated with increased B cell reactivity to phosphorylcholine, but reduced T15 idiotype dominance

AU - Khomtchouk, Kelly

AU - Alter, Sarah

AU - Ratliff, Michelle

AU - Blomberg, Bonnie B

AU - Riley, Richard L

PY - 2017/3/1

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N2 - 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.

AB - 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.

KW - Aging

KW - Immature B cells

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KW - Pre-B cell receptor

KW - Surrogate light chain

KW - T15 idiotype

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