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Decreased expression of tumor necrosis factor family receptors involved in humoral immune responses in preterm neonates
Abstract
Neonates have an increased rate of infection with encapsulated bacteria compared with older children and adults because of diminished antibody responses to T-independent (TI) antigens such as bacterial polysaccharides. Because the interactions of tumor necrosis factor (TNF) family ligands BAFF and APRIL with the TNF family receptors (TNFRs) TACI, BCMA, and BAFF-R are crucial to TI antibody responses, we measured the expression of these receptors on adult and cord blood–derived term and preterm neonatal B cells. Preterm neonatal B cells expressed less TACI, BCMA, and BAFF-R compared with adult B cells and had significantly less proliferation compared with adult B cells after stimulation with human recombinant BAFF and anti-IgM in an assay in which TACI-Fc fusion protein inhibits B-cell proliferation. In addition, neonatal dendritic cells had diminished expression of B7–1, B7–2, and CD40 compared with adult cells. Finally, neonatal B cells, particularly preterm B cells, exhibited markedly decreased production of IgG and IgA in response to CD40L and IL-10. Overall, this study shows that maturational delay in TNFR expression particularly by preterm neonatal B cells may interfere with effective antibody responses to TI antigens, cognate T- and B-cell interactions and normal isotype switching.
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“However, neonatal B cells express low levels of these co-receptors, limiting their capacity to respond [33].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [33]
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Metadata
- Authors
- Kaur, K., Chowdhury, S., Greenspan, N. S., & Schreiber, J. R.
- Affiliations
- University of Minnesota (US)
- Case Western Reserve University (US)
- ORCID
- Chowdhury, Shimul
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-10-15
- Volume
- 110
- Issue
- 8
- Pages
- 2948-2954
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2027616862
- Cited by
- 101
- References
- 50
- Citations by year
- 2026: 7 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 5 · 2017: 5 · 2016: 8 · 2015: 6 · 2014: 11 · 2013: 5 · 2012: 4
- FWCI
- 2.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Minnesota
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 32596, R01AI032596, AI 46661)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- preterm infants, BAFF, APRIL, TACI, BCMA, BAFF-R, B cells, dendritic cells, CD80, CD86, CD40, CD40 ligand, IL-10, IgG, IgA, class switch recombination, umbilical cord blood, neonatal immunity
- MeSH terms
- Adult, Antibody Formation, B-Lymphocytes, Dendritic Cells, Enzyme-Linked Immunosorbent Assay, Fetal Blood, Flow Cytometry, Humans, Immunoglobulin A, Immunoglobulin G, Infant, Newborn, Infant, Premature, Lymphocyte Activation, T-Lymphocytes, Gene Expression, Receptors, Tumor Necrosis Factor, Reverse Transcriptase Polymerase Chain Reaction, Cell Proliferation, B-Cell Activating Factor, Tumor Necrosis Factor Ligand Superfamily Member 13
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