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

Pinna, Debora; Corti, Davide; Jarrossay, David; Sallusto, Federica; Lanzavecchia, Antonio

doi:10.1002/eji.200839129

Cited by 194 publications

(196 citation statements)

References 43 publications

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“…The maximum of TT-specific PC and memory B cell numbers were observed on day 7 and day 14, respectively, after secondary immunization. This is in concordance with previous studies monitoring immune responses after TT (7,19) or influenza immunization (20,21). In these studies, peaks of Ag-specific PCs and memory B cells could be observed on days 6-8 and 14-28, respectively.…”

Section: Kineticssupporting

confidence: 92%

Secondary Immunization Generates Clonally Related Antigen-Specific Plasma Cells and Memory B Cells

Frölich

Giesecke

Mei

et al. 2010

The Journal of Immunology

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Rechallenge with T cell-dependent Ags induces memory B cells to re-enter germinal centers (GCs) and undergo further expansion and differentiation into plasma cells (PCs) and secondary memory B cells. It is currently not known whether the expanded population of memory B cells and PCs generated in secondary GCs are clonally related, nor has the extent of proliferation and somatic hypermutation of their precursors been delineated. In this study, after secondary tetanus toxoid (TT) immunization, TT-specific PCs increased 17- to 80-fold on days 6–7, whereas TT-specific memory B cells peaked (delayed) on day 14 with a 2- to 22-fold increase. Molecular analyses of VHDJH rearrangements of individual cells revealed no major differences of gene usage and CDR3 length between TT-specific PCs and memory B cells, and both contained extensive evidence of somatic hypermutation with a pattern consistent with GC reactions. This analysis identified clonally related TT-specific memory B cells and PCs. Within clusters of clonally related cells, sequences shared a number of mutations but also could contain additional base pair changes. The data indicate that although following secondary immunization PCs can derive from memory B cells without further somatic hypermutation, in some circumstances, likely within GC reactions, asymmetric mutation can occur. These results suggest that after the fate decision to differentiate into secondary memory B cells or PCs, some committed precursors continue to proliferate and mutate their VH genes.

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Section: Kineticssupporting

confidence: 92%

Secondary Immunization Generates Clonally Related Antigen-Specific Plasma Cells and Memory B Cells

Frölich

Giesecke

Mei

et al. 2010

The Journal of Immunology

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“…The response to CpG was not as pronounced, whether in the presence or absence of IL-2. The nonproliferating cells in these cultures were most probably the naive B cells [31]. Including anti-Ig showed that this, together with R848 and IL-2, induced the highest level of proliferation.…”

Section: The Cd21 -/Low B Cells Lack Expression Of the Abcb1 Transportermentioning

confidence: 83%

CD21–/low B cells in human blood are memory cells

Thorarinsdottir

Camponeschi

Cavallini

et al. 2016

Clinical and Experimental Immunology

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Summary The complement receptor 2 (CR2, CD21) is part of a complex (CD21/CD19/CD81) acting as a co‐receptor to the B cell receptor (BCR). Simultaneous triggering of the BCR and CD21 lowers the threshold for B cell activation. Although CD21 is important, B cells that express low amounts or lack surface CD21 (CD21–/low) are increased in conditions with chronic inflammation, e.g. autoimmune diseases. However, little is known about the CD21–/low B cell subset in peripheral blood from healthy donors. Here, we show that CD21–/low cells represent approximately 5% of B cells in peripheral blood from adults but are barely detectable in cord blood, after excluding transitional B cells. The CD21–/low subset can be divided into CD38–24+ and CD38–24low cells, where most of the CD38–24+ are CD27+immunoglobulin (Ig)M+IgD+ and the CD38–24low are switched CD27–. Expression levels of additional markers, e.g. CD95 and CD62L, are similar to those on classical memory B cells. In contrast to naive cells, the majority of CD21–/low cells lack expression of the ABCB1 transporter. Stimulation with a combination of BCR, Toll‐like receptor (TLR)−7/8 and interleukin (IL)−2 induces proliferation and differentiation of the CD21–/low B cells comparable to CD21+CD27+ memory B cells. The response excluding BCR agonist is not on par with that of classical memory B cells, although clearly above that of naive B cells. This is ascribed to a weaker response by the CD38–24low subset, implying that some memory B cells require not only TLR but also BCR triggering. We conclude that the CD21–/low cells in healthy donors are memory B cells.

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“…Nevertheless, these responses to benign microbes are mainly focused on the intestinal mucosa, unless the intestinal permeability barrier is breached and the live organism reaches systemic secondary lymphoid structures (Macpherson et al 2000;Konrad et al 2006). Weak systemic responses may be enough to induce polyclonal expansions (Zeng et al 2016), making pre-induced vaccine responses more durable (Pinna et al 2009), but are likely less ideal for de novo induction of systemic protective immunity unless one were to compromise by making the organism more invasive.…”

Section: Agitation Across Federal Borders: the Points Test For Differmentioning

confidence: 99%

Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens?

Macpherson

2017

Cold Spring Harb Perspect Biol

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In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign. This molecular cross talk is vital for the immune system to develop its mature form. Nevertheless, the microbiota/host biomass spaces are rather well separated: The microbiota also limits colonization and penetration of pathogens through intense metabolic competition. Immune responses to those members of the microbiota mutually adapted to intimate association at mucosal surfaces have attractive potential durability, but for clinical use as persistent vehicles they would require personalization and engineered reversibility to manage the immune context and complications in individual human subjects.GREAT DEBATES

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

Cited by 194 publications

References 43 publications

Secondary Immunization Generates Clonally Related Antigen-Specific Plasma Cells and Memory B Cells

Secondary Immunization Generates Clonally Related Antigen-Specific Plasma Cells and Memory B Cells

CD21–/low B cells in human blood are memory cells

Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens?

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