Inflammatory immune cells may impair the preBCR checkpoint, reduce new B cell production, and alter the antibody repertoire in old age

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1 Citation (Scopus)

Abstract

Aging impairs development of new B cells and diminishes the expression of protective antibodies. Reduced numbers of B cell precursors generally occur in old (~2 yrs.) mice. At the pro-B to pre-B cell transition, the pre-B cell receptor (preBCR) checkpoint directs pre-B cell expansion and selection of the pre-B cell immunoglobulin (Ig) μ heavy chain variable region repertoire. The preBCR is comprised of Ig μ heavy chain + surrogate light chains (SLC; λ5/VpreB). In old B cell precursors, SLC is decreased and fewer pre-B cells form the preBCR. In pro-B cells, SLC is complexed with cadherin 17 to form a “pro-B cell receptor” whose signaling is postulated to increase apoptotic sensitivity. We propose that inflammation in old mice, in part mediated by the age-associated B cells (ABC), promotes apoptosis among pro-B cells, particularly those relatively high in SLC. The remaining pro-B cells, with lower SLC, now generate pre-B cells with limited capacity to form the preBCR. Ig μ heavy chains vary in their capacity to associate with SLC and form the preBCR. We speculate that limited SLC restricts formation of the preBCR to a subset of Ig μ heavy chains. This likely impacts the composition of the antibody repertoire among B cells.

Original languageEnglish (US)
Pages (from-to)87-93
Number of pages7
JournalExperimental Gerontology
Volume105
DOIs
StatePublished - May 1 2018

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Pre-B Cell Receptors
B-Lymphoid Precursor Cells
Antibody Formation
B-Lymphocytes
Cells
Antibodies
Immunoglobulin Heavy Chains
Surrogate Immunoglobulin Light Chains
Cadherins

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

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title = "Inflammatory immune cells may impair the preBCR checkpoint, reduce new B cell production, and alter the antibody repertoire in old age",
abstract = "Aging impairs development of new B cells and diminishes the expression of protective antibodies. Reduced numbers of B cell precursors generally occur in old (~2 yrs.) mice. At the pro-B to pre-B cell transition, the pre-B cell receptor (preBCR) checkpoint directs pre-B cell expansion and selection of the pre-B cell immunoglobulin (Ig) μ heavy chain variable region repertoire. The preBCR is comprised of Ig μ heavy chain + surrogate light chains (SLC; λ5/VpreB). In old B cell precursors, SLC is decreased and fewer pre-B cells form the preBCR. In pro-B cells, SLC is complexed with cadherin 17 to form a “pro-B cell receptor” whose signaling is postulated to increase apoptotic sensitivity. We propose that inflammation in old mice, in part mediated by the age-associated B cells (ABC), promotes apoptosis among pro-B cells, particularly those relatively high in SLC. The remaining pro-B cells, with lower SLC, now generate pre-B cells with limited capacity to form the preBCR. Ig μ heavy chains vary in their capacity to associate with SLC and form the preBCR. We speculate that limited SLC restricts formation of the preBCR to a subset of Ig μ heavy chains. This likely impacts the composition of the antibody repertoire among B cells.",
author = "Riley, {Richard L} and Kelly Khomtchouk and Blomberg, {Bonnie B}",
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N2 - Aging impairs development of new B cells and diminishes the expression of protective antibodies. Reduced numbers of B cell precursors generally occur in old (~2 yrs.) mice. At the pro-B to pre-B cell transition, the pre-B cell receptor (preBCR) checkpoint directs pre-B cell expansion and selection of the pre-B cell immunoglobulin (Ig) μ heavy chain variable region repertoire. The preBCR is comprised of Ig μ heavy chain + surrogate light chains (SLC; λ5/VpreB). In old B cell precursors, SLC is decreased and fewer pre-B cells form the preBCR. In pro-B cells, SLC is complexed with cadherin 17 to form a “pro-B cell receptor” whose signaling is postulated to increase apoptotic sensitivity. We propose that inflammation in old mice, in part mediated by the age-associated B cells (ABC), promotes apoptosis among pro-B cells, particularly those relatively high in SLC. The remaining pro-B cells, with lower SLC, now generate pre-B cells with limited capacity to form the preBCR. Ig μ heavy chains vary in their capacity to associate with SLC and form the preBCR. We speculate that limited SLC restricts formation of the preBCR to a subset of Ig μ heavy chains. This likely impacts the composition of the antibody repertoire among B cells.

AB - Aging impairs development of new B cells and diminishes the expression of protective antibodies. Reduced numbers of B cell precursors generally occur in old (~2 yrs.) mice. At the pro-B to pre-B cell transition, the pre-B cell receptor (preBCR) checkpoint directs pre-B cell expansion and selection of the pre-B cell immunoglobulin (Ig) μ heavy chain variable region repertoire. The preBCR is comprised of Ig μ heavy chain + surrogate light chains (SLC; λ5/VpreB). In old B cell precursors, SLC is decreased and fewer pre-B cells form the preBCR. In pro-B cells, SLC is complexed with cadherin 17 to form a “pro-B cell receptor” whose signaling is postulated to increase apoptotic sensitivity. We propose that inflammation in old mice, in part mediated by the age-associated B cells (ABC), promotes apoptosis among pro-B cells, particularly those relatively high in SLC. The remaining pro-B cells, with lower SLC, now generate pre-B cells with limited capacity to form the preBCR. Ig μ heavy chains vary in their capacity to associate with SLC and form the preBCR. We speculate that limited SLC restricts formation of the preBCR to a subset of Ig μ heavy chains. This likely impacts the composition of the antibody repertoire among B cells.

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