Aging down-regulates the transcription factor e2a, activation-induced cytidine deaminase, and Ig class switch in human b cells

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Abstract

Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A -encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18-86 years). Our results obtained with activated CD19 + B cells show that the expression of E47, AID, and Igγl circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG +/IgA +), an increase in that of naive B cells (IgG -/IgA -/CD27 -) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans. The Journal of Immunology, 2008,

Original languageEnglish
Pages (from-to)5283-5290
Number of pages8
JournalJournal of Immunology
Volume180
Issue number8
StatePublished - Apr 15 2008

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B-Lymphocytes
Transcription Factors
Down-Regulation
Humoral Immunity
Vaccines
Immunoglobulin A
Genetic Recombination
Immunoglobulin Somatic Hypermutation
Immunoglobulin G
AICDA (activation-induced cytidine deaminase)
Allergy and Immunology
Cellular Immunity
Immunoglobulin M
Population

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Aging down-regulates the transcription factor e2a, activation-induced cytidine deaminase, and Ig class switch in human b cells",
abstract = "Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A -encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18-86 years). Our results obtained with activated CD19 + B cells show that the expression of E47, AID, and Igγl circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG +/IgA +), an increase in that of naive B cells (IgG -/IgA -/CD27 -) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans. The Journal of Immunology, 2008,",
author = "Daniela Frasca and Landin, {Ana Marie} and Lechner, {Suzanne C} and John Ryan and Robert Schwartz and Riley, {Richard L} and Blomberg, {Bonnie B}",
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T1 - Aging down-regulates the transcription factor e2a, activation-induced cytidine deaminase, and Ig class switch in human b cells

AU - Frasca, Daniela

AU - Landin, Ana Marie

AU - Lechner, Suzanne C

AU - Ryan, John

AU - Schwartz, Robert

AU - Riley, Richard L

AU - Blomberg, Bonnie B

PY - 2008/4/15

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N2 - Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A -encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18-86 years). Our results obtained with activated CD19 + B cells show that the expression of E47, AID, and Igγl circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG +/IgA +), an increase in that of naive B cells (IgG -/IgA -/CD27 -) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans. The Journal of Immunology, 2008,

AB - Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A -encoded transcription factor E47, which regulates many B cell functions, is down-regulated in old splenic B cells. This leads to a reduction in the activation-induced cytidine deaminase (AID), which is known to induce class switch recombination and Ig somatic hypermutation. The old activated murine B cells also have less AID and less switched Abs. We have extended our study here to investigate whether aging also affects Ab production and E47 and AID expression in B cells isolated from the peripheral blood of human subjects (18-86 years). Our results obtained with activated CD19 + B cells show that the expression of E47, AID, and Igγl circle transcripts progressively decrease with age. We also show an age-related decline in the percentage of switch memory B cells (IgG +/IgA +), an increase in that of naive B cells (IgG -/IgA -/CD27 -) for most individuals, and no decrease in that of IgM memory cells in peripheral blood, consistent with our data on the decrease seen in class switch recombination in vitro. Our results provide a possible molecular mechanism for a B cell intrinsic defect in the humoral immune response with aging and suggest avenues for improvement of vaccine response in elderly humans. The Journal of Immunology, 2008,

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