Isotype switching in human memory B cells sets intrinsic antigen-affinity thresholds that dictate antigen-driven fates
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ABSTRACT:
PROVIDER: PRJNA890611 | ENA |
REPOSITORIES: ENA
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Project description:Memory B cells (MBCs) play a critical role in protection against homologous and variant pathogen challenge by either differentiating to plasma cells (PCs) or to germinal center (GCs) B cells. The human MBC compartment contains both switched IgG+ and unswitched IgM+ MBCs and at present the contribution of these MBC subpopulations to protection is incompletely understood. We discovered that intrinsic antigen-affinity thresholds for activation were at least 100-fold higher for IgG+ as compared to IgM+ MBCs and that IgG+ MBCs when challenged responded only to high affinity antigens and differentiated almost exclusively towards PC fates. In contrast, IgM+ MBCs were eliminated by apoptosis by high affinity antigens and responded to low affinity antigens by differentiating towards GC B cell fates. Thus, IgG+ and IgM+ MBCs may play distinct yet complementary roles in response to pathogen challenge to ensure the immediate production of high affinity antibodies to homologous and closely related challenges and the generation of variant-specific MBCs through GC reactions.
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Project description:This SuperSeries is composed of the following subset Series: GSE38560: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (RNA-seq) GSE38561: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (ChIP-seq) GSE38562: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (genomic SEQ) GSE38563: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (MNase-seq) GSE38564: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (5) Refer to individual Series
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Project description:Bone marrow long-lived plasma cells are essential for long-term protection against infection and their persistence within this organ relies on interactions with Cxcl12-expressing stromal cells that are still not clearly identified. Here, using single cell RNAseq and in silico transinteractome analyses we identified LepR+ mesenchymal cells as the stromal cell subset most likely to interact with plasma cells within the bone marrow. Moreover, we demonstrated that depending on the isotype they express, plasma cells may use different set of integrins and adhesion molecules to interact with these stromal cells. Altogether, our results constitute an unprecedented characterization of plasma cell subset stromal niches and open new avenues for the specific targeting of bone marrow plasma cells based on their isotype.
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