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Regulation of Decay Accelerating Factor primes human germinal center B cells for phagocytosis

ABSTRACT: Regulation of Decay Accelerating Factor primes human germinal center B cells for phagocytosis

PROVIDER: PRJNA643839 | ENA |

REPOSITORIES: ENA

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Regulation of Decay Accelerating Factor primes human germinal center B cells for phagocytosis

Project description:Germinal centers (GCs) are structures in secondary lymphoid organs, essential for an efficient humoral immune response. Complement interaction with B cells facilitates B cell activation, but little is known about the role of complement regulators during B cell activation and differentiation. By flow cytometric analysis, we could show that the majority of human GC B cells had decreased expression of the negative complement regulator Decay Accelerating Factor (DAF). Transcriptomic analysis revealed that DAFlo GC B cells upregulated genes associated with gene editing and proliferation, whereas DAFhi GC B cells had increased expression of genes involved in cell differentiation. We could confirm that DAFhi GC B cells expressed the transcription factor Blimp1 on protein level, which indicates that DAFhi GC B cells may be early plasmablasts/plasma cells. Then, we assessed the expression of the complement regulator CD59, which inhibits the membrane attack complex that lyses cells. We found that the expression was low in naïve and memory B cells, but increased in GC and plasmablasts/plasma cells. This suggests that DAFlo GC B cells may be primed for phagocytosis rather than lysis. By cell sorting, we could show that DAFlo GC B cells were phagocytosed to a greater extent than DAFhi GC B cells, both in presence and absence of complement. Stimulation of the B cell receptor on circulating B cells induced DAFlo cells. Finally, we also identified specific downregulation of DAF during early B cell development in the human bone marrow. As a conclusion, we suggest that complement regulators serve specific functions at stages of B cell selection.

2020-12-31 | GSE153741 | GEO

Regulation of Decay Accelerating Factor Primes Human Germinal Center B Cells for Phagocytosis.

Project description:Germinal centers (GC) are sites for extensive B cell proliferation and homeostasis is maintained by programmed cell death. The complement regulatory protein Decay Accelerating Factor (DAF) blocks complement deposition on host cells and therefore also phagocytosis of cells. Here, we show that B cells downregulate DAF upon BCR engagement and that T cell-dependent stimuli preferentially led to activation of DAFlo B cells. Consistent with this, a majority of light and dark zone GC B cells were DAFlo and susceptible to complement-dependent phagocytosis, as compared with DAFhi GC B cells. We could also show that the DAFhi GC B cell subset had increased expression of the plasma cell marker Blimp-1. DAF expression was also modulated during B cell hematopoiesis in the human bone marrow. Collectively, our results reveal a novel role of DAF to pre-prime activated human B cells for phagocytosis prior to apoptosis.

| S-EPMC7813799 | biostudies-literature

Agents which upregulate CD55 [decay accelerating factor (DAF)] expression [Array]

Project description:Agents which upregulate CD55 [decay accelerating factor (DAF)] expression [Array]

| PRJNA1073479 | ENA

Transcriptomic analysis reveals the mechanism of watercore occurrence and its accelerating fruit decay

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B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection

Project description:B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection

| PRJNA936432 | ENA

Transcriptional profiling of mouse germinal center B cells (B220+, GL7+, CD95+) isolated from GC-specific (Cg1-Cre) DAF-TM transgenic or control mice

Project description:Germinal centers (GCs) support diversification and affinity maturation of antibody repertoires through iterative cycles of T-cell-dependent positive selection, B cell clonal expansion and antigen-receptor hypermutation. Positive selection is critical for efficient affinity maturation and depends on only partially understood signaling processes. We show that BCL6-dependent physiological repression of decay accelerating factor (DAF/CD55) on GC B cells is critical for effective positive selection and affinity maturation during GC responses. Absence of DAF on GC B cells lifts restraint on local complement activation, yielding autocrine C3a/C5a-receptor signaling that is indispensable for CD40-dependent mTOR pathway activation during positive selection. Genetic disruption of this pathway causes premature GC collapse and impairs affinity maturation. These results identify previously undiscerned targets to therapeutically manipulate protective and potentially injurious humoral immune responses.

2021-03-22 | GSE148570 | GEO

Proteome profiling of mouse germinal center B cells

Project description:Productive B cell responses are critical to protect a host from infection. The spleen and lymph nodes are populated by resting follicular B cells, which can enter germinal centers upon antigen encounter. Once in the germinal center, B cells migrate between the dark and light zones, where they undergo somatic hypermutation and selection, respectively. While germinal center B cells have been studied, an intense molecular understanding of these cells/subsets (and the differences between them) is lacking.

2020-04-06 | PXD015524 | Pride

B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [bulk RNA-seq]

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Accelerating Medicines Partnership-Rheumatoid Arthritis (AMP-RA)

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B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [single cell RNA-Seq]

Project description:B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [single cell RNA-Seq]

| PRJNA936433 | ENA