ArticleThe Journal of experimental medicine1998
In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. V. Affinity maturation develops in two stages of clonal selection.
Article in The Journal of experimental medicine, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
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Who cites it
143 citing papers in PubMed, 339 citations in OpenAlex.
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- Recall of B cell memory depends on relative locations of prime and boost immunization.Science immunology · 2022Article
- Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5Immunity · 2022Article
- Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination.Frontiers in immunology · 2022Article
- Follicular dendritic cell dysfunction contributes to impaired antigen-specific humoral responses in sepsis-surviving mice.The Journal of clinical investigation · 2021Article
- Minimalistic In Vitro Culture to Drive Human Naive B Cell Differentiation into Antibody-Secreting Cells.Cells · 2021Article
- Analysis of Somatic Hypermutation in the JH4 intron of Germinal Center B cells from Mouse Peyer's Patches.Journal of visualized experiments : JoVE · 2021Article
- Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Efficient homing of antibody-secreting cells to the bone marrow requires RNA-binding protein ZFP36L1.The Journal of experimental medicine · 2021Article
- Memory B Cells in Pregnancy Sensitization.Frontiers in immunology · 2021Review
- Robust Plasma Cell Response to Skin-Inoculated Dengue Virus in Mice.Journal of immunology research · 2021Article
83 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
To examine the role of germinal centers (GCs) in the generation and selection of high affinity antibody-forming cells (AFCs), we have analyzed the average affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific AFCs and serum antibodies both during and after the GC phase of the immune response. In addition, the genetics of NP-binding AFCs were followed to monitor the generation and selection of high affinity AFCs at the clonal level. NP-binding AFCs gradually accumulate in bone marrow (BM) after immunization and BM becomes the predominant locale of specific AFCs in the late primary response. Although the average affinity of NP-specific BM AFCs rapidly increased while GCs were present (GC phase), the affinity of both BM AFCs and serum antibodies continued to increase even after GCs waned (post-GC phase). Affinity maturation in the post-GC phase was also reflected in a shift in the distribution of somatic mutations as well as in the CDR3 sequences of BM AFC antibody heavy chain genes. Disruption of GCs by injection of antibody specific for CD154 (CD40 ligand) decreased the average affinity of subsequent BM AFCs, suggesting that GCs generate the precursors of high affinity BM AFCs; inhibition of CD154-dependent cellular interactions after the GC reaction was complete had no effect on high affinity BM AFCs. Interestingly, limited affinity maturation in the BM AFC compartment still occurs during the late primary response even after treatment with anti-CD154 antibody. Thus, GCs are necessary for the generation of high affinity AFC precursors but are not the only sites for the affinity-driven clonal selection responsible for the maturation of humoral immune responses.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.