Publication: Altered marginal zone and innate-like B cells in aged senescence-accelerated SAMP8 mice with defective IgG1 responses
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2017-08-17
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Cortegano, Isabel ISCIII 
Rodriguez-Garcia, Mercedes ISCIII
Prado-Zamora, Maria Carmen ISCIII
Ruiz, Carolina ISCIII
Hortigüela, Rafael ISCIII
Alia, Mario ISCIII 
Vilar, Marçal ISCIII
Cano, Eva ISCIII
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Nature Publishing Group
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Abstract
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19+CD45R+CD21++CD23lo) and a decrease of naive B cells (CD19+IgD+), whereas there is an enhancement of a CD19+CD45Rlo innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R+CD21loCD23loCD5-CD11b-) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice. These changes in aged SAMP8 mice were associated with lower IgG isotype levels, displaying low variable gene usage repertoires of the immunoglobulin heavy chain (VH) diversity, with a diminution on IgG1-memory B cells (CD11b-Gr1-CD138-IgM-IgD-CD19+CD38+IgG1+), an increase in T follicular helper (TFH, CD4+CXCR5+PD1+) cell numbers, and an altered MOMA-1 (metallophilic macrophages) band in primary follicles. LPS-mediated IgG1 responses were impaired in the B1REL and ABC cell compartments, both in vitro and in vivo. These data demonstrate the prominent changes to different B cell populations and in structural follicle organization that occur upon aging in SAMP8 mice. These novel results raise new questions regarding the importance of the cellular distribution in the B cell layers, and their effector functions needed to mount a coordinated and effective humoral response.
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Aging Animals Antigens, CD B-Lymphocytes Cell Death Cell Proliferation Gene Expression Regulation, Developmental IgG Deficiency Immunity, Humoral Immunity, Innate Immunoglobulin D Immunoglobulin A Immunoglobulin Heavy Chains Immunoglobulin M Immunologic Memory Lipopolysaccharides Mice, Inbred BALB Mice, Transgenic Primary Cell Culture Signal Transduction Spleen T-Lymphocytes, Helper-Inducer
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Bibliographic citation
Cell Death Dis. 2017 Aug 17;8(8):e3000.