Long-Lived Plasma Cells in Mice and Men

Brynjólfsson, Siggeir F.; Berg, Linn Persson; Ekerhult, Teresa Olsen; Rimkutė, Inga; Wick, Mary-Jo; Mårtensson, Inga‐Lill; Grimsholm, Ola

doi:10.3389/fimmu.2018.02673

Cited by 90 publications

(76 citation statements)

References 92 publications

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“…). Multidimensional analysis of B cells was based on the expression of B220 (pan‐B cell marker in the mouse) , CD38 (highly expressed on mature and memory B cells, while it is reduced to an intermediate expression in germinal center B cells) , GL7 and CD95 (coexpressed by B cells involved in the GC reaction) , CD73 (memory B cells) , IgG1 and IgM (B cell receptors (BCR) in switched or unswitched B cells, respectively) , TACI and CD138 (coexpressed by terminally differentiated PCs) and CXCR4 (chemokine receptor involved in long‐lived PCs homing into bone marrow niches) . The flow of the process (Fig.…”

Section: Resultsmentioning

confidence: 99%

Computational Analysis of Multiparametric Flow Cytometric Data to Dissect B Cell Subsets in Vaccine Studies

et al. 2019

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The generation of the B cell response upon vaccination is characterized by the induction of different functional and phenotypic subpopulations and is strongly dependent on the vaccine formulation, including the adjuvant used. Here, we have profiled the different B cell subsets elicited upon vaccination, using machine learning methods for interpreting high‐dimensional flow cytometry data sets. The B cell response elicited by an adjuvanted vaccine formulation, compared to the antigen alone, was characterized using two automated methods based on clustering (FlowSOM) and dimensional reduction (t‐SNE) approaches. The clustering method identified, based on multiple marker expression, different B cell populations, including plasmablasts, plasma cells, germinal center B cells and their subsets, while this profiling was more difficult with t‐SNE analysis. When undefined phenotypes were detected, their characterization could be improved by integrating the t‐SNE spatial visualization of cells with the FlowSOM clusters. The frequency of some cellular subsets, in particular plasma cells, was significantly higher in lymph nodes of mice primed with the adjuvanted formulation compared to antigen alone. Thanks to this automatic data analysis it was possible to identify, in an unbiased way, different B cell populations and also intermediate stages of cell differentiation elicited by immunization, thus providing a signature of B cell recall response that can be hardly obtained with the classical bidimensional gating analysis. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

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Section: Resultsmentioning

confidence: 99%

Computational Analysis of Multiparametric Flow Cytometric Data to Dissect B Cell Subsets in Vaccine Studies

et al. 2019

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“…When naïve B cells are activated after the encounter with their cognate antigen, they become either memory B cells or plasma cells (PCs), which can be short-or long-lived PCs (SLPCs and LLPCs) [63]. While the magnitude of early humoral responses is determined by both types of PCs, the long-term maintenance of antibodies is antigen-independent and could last for life [28,63,64], due to the continuous presence of LLPCs. Whether these are the same PCs generated at priming or are rather derived from the differentiation of memory B cells into "new" LLPCs is not clear yet.…”

Section: Discussionmentioning

confidence: 99%

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

et al. 2020

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Human papillomavirus (HPV) persistent infections are associated with cervical cancer and other HPV-related diseases and tumors. Thus, the characterization of long lasting immunity to currently available HPV vaccines is important. A total of 149 female subjects vaccinated with Cervarix or Gardasil participated to the study and they were stratified according to age (10–12-year-old and 16–20-year-old). Humoral immune responses (IgG and neutralizing antibody titers, antibody avidity) and circulating memory B cells were analyzed after an average of 4–6 years from the third immunization. The humoral responses against HPV-16 and HPV-18 (and HPV-6 and HPV-11 for Gardasil) were high in both age groups and vaccines up to six years from the third dose. However, Cervarix induced significantly higher and more persistent antibody responses, while the two vaccines were rather equivalent in inducing memory B cells against HPV-16 and HPV-18. Moreover, the percentage of subjects with vaccine-specific memory B cells was even superior among Gardasil vaccinees and, conversely, Cervarix vaccinated individuals with circulating antibodies, but undetectable memory B cells were found. Finally, a higher proportion of Cervarix-vaccinated subjects displayed cross-neutralizing responses against non-vaccine types HPV-31 and HPV-45. Gardasil and Cervarix may, thus, differently affect long-lasting humoral immunity from both the quantitative and qualitative point of view.

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“…It is well established that long-lasting protective antibody responses require the generation of antibody-secreting long-lived plasma cells (LLPCs) (5) and memory B cells (MBCs), that rapidly differentiate into plasmablasts upon rechallenge (6). However, studies of children in endemic areas suggest that the response to malaria is dominated by short-lived plasma cells rather than LLPCs (reviewed in (3)) and that Pf-specific MBCs are acquired relatively inefficiently (3,7).…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM

Hopp

Diouf

Miura

et al. 2020

Preprint

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IgG antibodies are known to play a central role in naturally acquired immunity to blood-stage malaria in humans, but little is known about the IgM response to blood-stage malaria, the mechanisms by which IgM may protect, or the underlying biology of Plasmodium falciparum (Pf)-specific IgM B cells. In a Mali cohort spanning infants to adults we conducted a longitudinal analysis of B cells specific for the Pf blood-stage antigens AMA1 and MSP1, as well as the comparator antigen influenza hemagglutinin (HA). At the uninfected baseline, before the malaria season, Pf-specific memory B cells (MBCs) in children are disproportionally IgM + and only gradually shift to IgG + with age, in contrast to HA-specific MBCs that are predominantly IgG + from infancy to adulthood. In response to acute febrile malaria, Pf-specific IgM B cells increase in frequency and upregulate activation and co-stimulatory markers. B cell receptor (BCR) analysis showed that Pf-specific IgM B cells are somatically hypermutated at levels comparable to HA-specific IgG B cells. Finally, IgM antibodies from the plasma of malaria-exposed individuals were comparable to IgG in inhibiting Pf blood-stage growth in vitro, and significantly better at enhancing phagocytosis of Pf merozoites, suggesting that IgM may protect through both direct neutralization and opsonization. Thus, somatically hypermutated Pf-specific IgM MBCs dominate in early life, are activated and expand during acute malaria and are associated with plasma IgM that inhibits parasite growth in vitro.

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Long-Lived Plasma Cells in Mice and Men

Cited by 90 publications

References 92 publications

Computational Analysis of Multiparametric Flow Cytometric Data to Dissect B Cell Subsets in Vaccine Studies

Computational Analysis of Multiparametric Flow Cytometric Data to Dissect B Cell Subsets in Vaccine Studies

HPV-Specific Systemic Antibody Responses and Memory B Cells are Independently Maintained up to 6 Years and in a Vaccine-Specific Manner Following Immunization with Cervarix and Gardasil in Adolescent and Young Adult Women in Vaccination Programs in Italy

Plasmodium falciparum-specific IgM B cells dominate in children, expand with malaria and produce parasite inhibitory IgM

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