Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

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Abstract

We previously demonstrated that in vitro stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes, class switch recombination (CSR), induction of the E2A-encoded transcription factor E47, and activation-induced cytidine deaminase (AID) which is necessary for CSR and somatic hypermutation. Both anti-CD40 as well as BAFF have been shown to be able to induce CSR. We have investigated the ability of BAFF/IL-4, as compared to anti-CD40/IL-4, to induce CSR to γ1 in splenic B cells from young and old mice. We found that anti-CD40/IL-4 is a better CSR stimulus than BAFF/IL-4 in young B cells, as measured by RT-PCR of post-switch transcripts and flow cytometry. CSR is reduced in old B cells and this is independent of the stimulus. AID and γ1PSTs are significantly reduced in old B cells stimulated with anti-CD40/IL-4, but only slightly reduced with BAFF/IL-4. BAFF receptor mRNA expression (BAFF-R, TACI, and BCMA) is not affected by aging. The age-related decrease in CSR induced by anti-CD40/IL-4 is primarily associated with a decrease in E47, whereas the less affected response to BAFF/IL-4 is associated with decreases in both E47 and NF-κB. Therefore, NF-κB is not involved in the decreased response of old B cells to anti-CD40/IL-4. These differences in B cell responses to CD40/IL-4 and BAFF/IL-4 may help to explain the maintenance of TI vs TD responses in senescent mice.

Original languageEnglish
Pages (from-to)192-203
Number of pages12
JournalExperimental Gerontology
Volume42
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Interleukin-4
B-Lymphocytes
Aging of materials
Cells
Switches
Genetic Recombination
B-Cell Activation Factor Receptor
Flow cytometry
Transcriptional Activation
Flow Cytometry
Transcription Factors
Maintenance
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Aging
  • AID
  • B cells
  • BAFF
  • Class switch recombination

ASJC Scopus subject areas

  • Aging
  • Medicine(all)

Cite this

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title = "Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF",
abstract = "We previously demonstrated that in vitro stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes, class switch recombination (CSR), induction of the E2A-encoded transcription factor E47, and activation-induced cytidine deaminase (AID) which is necessary for CSR and somatic hypermutation. Both anti-CD40 as well as BAFF have been shown to be able to induce CSR. We have investigated the ability of BAFF/IL-4, as compared to anti-CD40/IL-4, to induce CSR to γ1 in splenic B cells from young and old mice. We found that anti-CD40/IL-4 is a better CSR stimulus than BAFF/IL-4 in young B cells, as measured by RT-PCR of post-switch transcripts and flow cytometry. CSR is reduced in old B cells and this is independent of the stimulus. AID and γ1PSTs are significantly reduced in old B cells stimulated with anti-CD40/IL-4, but only slightly reduced with BAFF/IL-4. BAFF receptor mRNA expression (BAFF-R, TACI, and BCMA) is not affected by aging. The age-related decrease in CSR induced by anti-CD40/IL-4 is primarily associated with a decrease in E47, whereas the less affected response to BAFF/IL-4 is associated with decreases in both E47 and NF-κB. Therefore, NF-κB is not involved in the decreased response of old B cells to anti-CD40/IL-4. These differences in B cell responses to CD40/IL-4 and BAFF/IL-4 may help to explain the maintenance of TI vs TD responses in senescent mice.",
keywords = "Aging, AID, B cells, BAFF, Class switch recombination",
author = "Daniela Frasca and Riley, {Richard L} and Blomberg, {Bonnie B}",
year = "2007",
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doi = "10.1016/j.exger.2006.09.003",
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T1 - Aging murine B cells have decreased class switch induced by anti-CD40 or BAFF

AU - Frasca, Daniela

AU - Riley, Richard L

AU - Blomberg, Bonnie B

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N2 - We previously demonstrated that in vitro stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes, class switch recombination (CSR), induction of the E2A-encoded transcription factor E47, and activation-induced cytidine deaminase (AID) which is necessary for CSR and somatic hypermutation. Both anti-CD40 as well as BAFF have been shown to be able to induce CSR. We have investigated the ability of BAFF/IL-4, as compared to anti-CD40/IL-4, to induce CSR to γ1 in splenic B cells from young and old mice. We found that anti-CD40/IL-4 is a better CSR stimulus than BAFF/IL-4 in young B cells, as measured by RT-PCR of post-switch transcripts and flow cytometry. CSR is reduced in old B cells and this is independent of the stimulus. AID and γ1PSTs are significantly reduced in old B cells stimulated with anti-CD40/IL-4, but only slightly reduced with BAFF/IL-4. BAFF receptor mRNA expression (BAFF-R, TACI, and BCMA) is not affected by aging. The age-related decrease in CSR induced by anti-CD40/IL-4 is primarily associated with a decrease in E47, whereas the less affected response to BAFF/IL-4 is associated with decreases in both E47 and NF-κB. Therefore, NF-κB is not involved in the decreased response of old B cells to anti-CD40/IL-4. These differences in B cell responses to CD40/IL-4 and BAFF/IL-4 may help to explain the maintenance of TI vs TD responses in senescent mice.

AB - We previously demonstrated that in vitro stimulated splenic B cells from senescent mice are deficient in production of multiple class switch isotypes, class switch recombination (CSR), induction of the E2A-encoded transcription factor E47, and activation-induced cytidine deaminase (AID) which is necessary for CSR and somatic hypermutation. Both anti-CD40 as well as BAFF have been shown to be able to induce CSR. We have investigated the ability of BAFF/IL-4, as compared to anti-CD40/IL-4, to induce CSR to γ1 in splenic B cells from young and old mice. We found that anti-CD40/IL-4 is a better CSR stimulus than BAFF/IL-4 in young B cells, as measured by RT-PCR of post-switch transcripts and flow cytometry. CSR is reduced in old B cells and this is independent of the stimulus. AID and γ1PSTs are significantly reduced in old B cells stimulated with anti-CD40/IL-4, but only slightly reduced with BAFF/IL-4. BAFF receptor mRNA expression (BAFF-R, TACI, and BCMA) is not affected by aging. The age-related decrease in CSR induced by anti-CD40/IL-4 is primarily associated with a decrease in E47, whereas the less affected response to BAFF/IL-4 is associated with decreases in both E47 and NF-κB. Therefore, NF-κB is not involved in the decreased response of old B cells to anti-CD40/IL-4. These differences in B cell responses to CD40/IL-4 and BAFF/IL-4 may help to explain the maintenance of TI vs TD responses in senescent mice.

KW - Aging

KW - AID

KW - B cells

KW - BAFF

KW - Class switch recombination

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