Control of memory B cell responses by extrinsic and intrinsic mechanisms

Wienands, Jürgen; Engels, Niklas

doi:10.1016/j.imlet.2016.05.010

Cited by 8 publications

(4 citation statements)

References 33 publications

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“…One area of recent progress is the differences in signaling between IgM and IgG BCRs (150). An emerging body of work has shown that all IgG BCRs allow for inducible phosphorylation on a tyrosine residue in a motif termed the immunoglobulin tail tyrosine (ITT) motif.…”

Section: Differences In Mbc Signalingmentioning

confidence: 99%

Memory B Cells of Mice and Humans

Weisel

Shlomchik²

2017

Annu. Rev. Immunol.

239

249

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We comprehensively review memory B cells (MBCs), covering the definition of MBCs and their identities and subsets, how MBCs are generated, where they are localized, how they are maintained, and how they are reactivated. Whereas naive B cells adopt multiple fates upon stimulation, MBCs are more restricted in their responses. Evolving work reveals that the MBC compartment in mice and humans consists of distinct subpopulations with differing effector functions. We discuss the various approaches to define subsets and subset-specific roles. A major theme is the need to both deliver faster effector function upon reexposure and readapt to antigenically variant pathogens while avoiding burnout, which would be the result if all MBCs generated only terminal effector function. We discuss cell-intrinsic differences in gene expression and signaling that underlie differences in function between MBCs and naive B cells and among MBC subsets and how this leads to memory responses.

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Section: Differences In Mbc Signalingmentioning

confidence: 99%

Memory B Cells of Mice and Humans

Weisel

Shlomchik²

2017

Annu. Rev. Immunol.

239

249

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“…While many human and murine memory B cells still express IgM, a significant proportion has already switched to the production of downstream antibody subclasses, mainly IgA and IgGs ( 29 – 31 ). Antigen-mediated crosslinking of membrane IgG provides a much stronger activation signal than IgM ( 32 ), which contributes to the reduced activation threshold observed for memory B cells and their capacity to quickly give rise to antibody-secreting plasma cells ( 33 – 36 ). Independent from their subclass, memory B cells have down-regulated the expression of genes that negatively control BCR signaling and have up-regulated the expression of their counterparts ( 37 , 38 ).…”

Section: B Cells Plasma Cells and Their Impact On Autoimmune Diseasmentioning

confidence: 99%

Targeting B Cells and Plasma Cells in Autoimmune Diseases

2018

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Success with B cell depletion using rituximab has proven the concept that B lineage cells represent a valid target for the treatment of autoimmune diseases, and has promoted the development of other B cell targeting agents. Present data confirm that B cell depletion is beneficial in various autoimmune disorders and also show that it can worsen the disease course in some patients. These findings suggest that B lineage cells not only produce pathogenic autoantibodies, but also significantly contribute to the regulation of inflammation. In this review, we will discuss the multiple pro- and anti-inflammatory roles of B lineage cells play in autoimmune diseases, in the context of recent findings using B lineage targeting therapies.

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“…Long-lived humoral immunity is realized through the joint functions of memory B cells (MBCs) and plasma cells (PCs). Naïve B cells (nBs) and MBCs have similar fates upon T-dependent stimulation although MBCs respond more quickly and with greater magnitude to antigenic challenge (1,2). For the most part, MBCs tend to be affinity matured with class-switched BCRs (3)(4)(5) and gain unique surface markers, such as CD73, PD-L2, and CD80 (6,7).…”

Section: Introductionmentioning

confidence: 99%

“…Mt1 plays a role in iron ion homeostasis(42), and Pik3r6 regulates phosphoinositide 3-kinase signaling, which is activated downstream of BCR triggering(43). The unique expression of Pik3r6 in IgG MBCs suggests a differential role for this protein downstream of IgM and IgG BCRs(2,3). Further functional exploration of the DEG using gene set enrichment analysis (GSEA) (44) identified that cell cycle genes were upregulated in IgG MBCs compared to both IgM MBCs and nBs, underscoring their rapid responses to stimulation (Fig.2J).…”

mentioning

confidence: 99%

Conserved Epigenetic Programming and Enhanced Heme Metabolism Drive Memory B Cell Reactivation

Price

Scharer

Kania

et al. 2021

The Journal of Immunology

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Memory B cells (MBCs) have enhanced capabilities to differentiate to plasma cells and generate a rapid burst of antibodies upon secondary stimulation. To determine if MBCs harbor an epigenetic landscape that contributes to increased differentiation potential, we derived the chromatin accessibility and transcriptomes of influenza-specific IgM and IgG MBCs compared to naïve cells. MBCs possessed an accessible chromatin architecture surrounding plasma cell specific genes, as well as altered expression of transcription factors and genes encoding cell cycle, chemotaxis, and signal transduction processes. Intriguingly, this MBC signature was conserved between humans and mice. MBCs of both species possessed a heightened heme signature compared to naïve cells. Differentiation in the presence of hemin enhanced oxidative phosphorylation metabolism and MBC differentiation into antibody secreting plasma cells. Thus, these data define conserved MBC transcriptional and epigenetic signatures that include a central role for heme and multiple other pathways in augmenting MBC reactivation potential.

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Control of memory B cell responses by extrinsic and intrinsic mechanisms

Cited by 8 publications

References 33 publications

Memory B Cells of Mice and Humans

Memory B Cells of Mice and Humans

Targeting B Cells and Plasma Cells in Autoimmune Diseases

Conserved Epigenetic Programming and Enhanced Heme Metabolism Drive Memory B Cell Reactivation

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