B cell antigen presentation in the initiation of follicular helper T cell and germinal center differentiation
Open accessAbstract
High-affinity class-switched Abs and memory B cells are products of the germinal center (GC). The CD4+ T cell help required for the development and maintenance of the GC is delivered by follicular Th cells (TFH), a CD4+ Th cell subset characterized by expression of Bcl-6 and secretion of IL-21. The cellular interactions that mediate differentiation of TFH and GC B cells remain an important area of investigation. We previously showed that MHC class II (MHCII)–dependent dendritic cell Ag presentation is sufficient for the differentiation of a TFH intermediate (termed pre-TFH), characterized by Bcl-6 expression but lacking IL-21 secretion. In this article, we examine the contributions of MHCII Ag presentation by B cells to TFH differentiation and GC responses in several contexts. B cells alone do not efficiently prime naive CD4+ T cells or induce TFH after protein immunization; however, during lymphocytic choriomeningitis virus infection, B cells induce TFH differentiation despite the lack of effector CD4+ T cell generation. Still, MHCII+ dendritic cells and B cells cooperate for optimal TFH and GC B cell differentiation in response to both model Ags and viral infection. This study highlights the roles for B cells in both CD4+ T cell priming and TFH differentiation, and demonstrates that different APC subsets work in tandem to mediate the GC response.
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After vaccination, T follicular helper cells are less frequent in older subjects and appear to malfunction.
“after vaccination, T follicular helper (Tfh) cells are less frequent in older subjects and appear to be malfunctioning”
From Successful and Maladaptive T Cell Aging (2017) · cites this paper as Barnett et al., 2014
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- Authors
- Barnett, L. G., Simkins, H. M. A., Barnett, B. E., Korn, L. L., Johnson, A. L., Wherry, E. J., Wu, G. F., & Laufer, T. M.
- Affiliations
- University of Pennsylvania (US)
- Washington University in St. Louis (US)
- Veterans Health Administration (US)
- Corresponding author
- Laufer, Terri M
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-04
- Volume
- 192
- Issue
- 8
- Pages
- 3607-3617
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC4380085
- OpenAlex
- W2153049166
- Cited by
- 123
- References
- 70
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 8 · 2023: 4 · 2022: 10 · 2021: 11 · 2020: 8 · 2019: 14 · 2018: 15 · 2017: 16 · 2016: 9 · 2015: 8 · 2014: 4
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX000435)
- Dana Foundation
- National Institutes of Health (HHSN266200500030C, AI082630, AI083022, AI045008, AI095608)
- National Institute of Allergy and Infectious Diseases (HHSN266200500030C, AI 082630, R01AI105343, AI095608, U19AI083022, AI 083005, T32AI007632, U01AI083005, AI045008, AI 083022, U01AI095776, AI095776, U01AI095608, U19AI082630, P30AI045008)
- National Institute of Neurological Disorders and Stroke (K08NS062138)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32 AR 0077442)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Keywords
- T follicular helper cells, germinal center, B cell antigen presentation, MHC class II, dendritic cells, BCL6, IL-21, CD4+ T cell priming, lymphocytic choriomeningitis virus, germinal center B cells
- MeSH terms
- Animals, Antigens, B-Lymphocytes, Cell Differentiation, Dendritic Cells, H-2 Antigens, T-Lymphocytes, Helper-Inducer, Immunization, Virus Diseases, CD4-Positive T-Lymphocytes, Antigen Presentation, Mice, Knockout, Germinal Center, T-Lymphocytes, Regulatory, Mice
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