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Clonal dissection of the human memory B-cell repertoire following infection and vaccination.

ABSTRACT: The analysis of the human memory B-cell repertoire is of both fundamental and practical significance. We developed a simple method for the selective activation of memory B cells in total fresh or frozen PBMC using a combination of R848 and IL-2. In these conditions, 30-40% of memory B cells generated clones producing on average 200 ng IgG in 10 days. This method was used to measure the frequency of antigen-specific memory B cells as well as the fine specificity, cross-reactivity and neutralizing activity of the secreted antibodies. Following influenza vaccination, specific B cells expanded dramatically, reaching up to 50% of total clonable memory B cells on day 14. Specific B-cell expansions were detected also in individuals that did not show a significant serological response. Dynamic changes and persistence of B cells specific for a variety of pathogens were documented in serial PBMC samples collected over almost two decades. These results reveal novel aspects of memory B-cell kinetics and provide a powerful tool to monitor immune responses following infection and vaccination.

SUBMITTER: Pinna D

PROVIDER: S-EPMC3864550 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Clonal dissection of the human memory B-cell repertoire following infection and vaccination.

Pinna Debora D Corti Davide D Jarrossay David D Sallusto Federica F Lanzavecchia Antonio A

European journal of immunology 20090501 5

The analysis of the human memory B-cell repertoire is of both fundamental and practical significance. We developed a simple method for the selective activation of memory B cells in total fresh or frozen PBMC using a combination of R848 and IL-2. In these conditions, 30-40% of memory B cells generated clones producing on average 200 ng IgG in 10 days. This method was used to measure the frequency of antigen-specific memory B cells as well as the fine specificity, cross-reactivity and neutralizing ...[more]

PMID: 19404981

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Project description:Recent functional, gene expression, and epigenetic studies have suggested the presence of a subset of mature natural killer (NK) cells responsible for maintaining NK cell memory. The lack of endogenous clonal markers in NK cells impedes understanding the genesis of these cell populations. In humans, primates, and mice, this phenotype and memory or adaptive functions have been strongly linked to cytomegalovirus or related herpes virus infections. We have used transplantation of lentivirally-barcoded autologous hematopoietic stem and progenitor cells (HSPC) to track clonal hematopoiesis in rhesus macaques and previously reported striking oligoclonal expansions of NK-biased barcoded clones within the CD56-CD16+ NK cell subpopulation, clonally distinct from ongoing output of myeloid, B cell, T cell, and CD56+16- NK cells from HSPC. These CD56-CD16+ NK cell clones segregate by expression of specific KIR surface receptors, suggesting clonal expansion in reaction to specific environmental stimuli. We have now used this model to investigate the impact of rhesus CMV(RhCMV) infection on NK clonal dynamics. Following transplantation, RhCMVneg rhesus macaques display less dominant and oligoclonal CD16+ NK cells biased clones compared to RhCMVpos animals, however these populations of cells are still clearly present. Upon RhCMV infection, CD16+ NK cells proliferate, followed by appearance of new groups of expanded NK clones and disappearance of clones present prior to RhCMV infection. A second superinfection with RhCMV resulted in rapid viral clearance without major change in the mature NK cell clonal landscape. Our findings suggest that RhCMV is not the sole driver of clonal expansion and peripheral maintenance of mature NK cells; however, infection of macaques with this herpesvirus does result in selective expansion and persistence of specific NK cell clones, providing further information relevant to adaptive NK cells and the development of NK cell therapies.

Project description:As of March 2022, there have been over 450 million reported SARS-CoV-2 cases worldwide, and more than 4 billion people have received their primary series of a COVID-19 vaccine. In order to longitudinally track SARS-CoV-2 antibody levels in people after vaccination or infection, a large-scale COVID-19 sero-surveillance progam entitled SPARTA (SeroPrevalence and Respiratory Tract Assessment) was established early in the pandemic. Anti-RBD antibody levels were tracked in more than 1,000 people. There was no significant decrease in antibody levels during the first 14 months after infection in unvaccinated participants, however, significant waning of antibody levels was observed following vaccination, regardless of previous infection status. Moreover, participants who were pre-immune to SARS-CoV-2 prior to vaccination seroconverted to significantly higher antibody levels, and antibodies were maintained at significantly higher levels than in previously infected, unvaccinated participants. This pattern was entirely due to differences in the magnitude of the initial seroconversion event, and the rate of antibody waning was not significantly different based on the pre-immune status. Participants who received a third (booster) dose of an mRNA vaccine not only increased their anti-RBD antibody levels ∼14-fold, but they also had ∼3 times more anti-RBD antibodies compared to the peak of their antibody levels after receiving their primary vaccine series. In order to ascertain whether the presence of serum antibodies is important for long-term seroprotection, PBMCs from 13 participants who lost all detectable circulating antibodies after vaccination or infection were differentiated into memory cells in vitro . There was a significant recall of memory B cells in the absence of serum antibodies in 70% of the vaccinated participants, but not in any of the infected participants. Therefore, there is a strong connection between anti-RBD antibody levels and the effectiveness of memory B cell recall.

Dataset Information

Clonal dissection of the human memory B-cell repertoire following infection and vaccination.

Publications

Clonal dissection of the human memory B-cell repertoire following infection and vaccination.

Similar Datasets

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