Impact of IgA vs IgM BCR expression
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB88673 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR14860787_1.fastq.gz | Fastqsanger.gz | |||
| ERR14860787_2.fastq.gz | Fastqsanger.gz | |||
| ERR14860788_1.fastq.gz | Fastqsanger.gz | |||
| ERR14860788_2.fastq.gz | Fastqsanger.gz | |||
| ERR14860789_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:MZB1 is an endoplasmic reticulum residential protein preferentially expressed in plasma cells, marginal zone and B1 B cells. Recent studies on murine B cells shows that it interacts with the tail piece of IgM and IgA heavy chain and promotes the secretion of these two classes of immunoglobulin. However, its role in primary human B cells has yet to be determined and how its function is regulated is still unknown. The conversion of peptidylarginine to peptidycitrulline, also known as citrullination, by peptidylarginine deiminases (PADs) can critically influence the function of proteins in immune cells, such as neutrophils and T cells; however, the role of PADs in B cells remains to be elucidated. In an unbiased analysis of the human citrullinomeic analysis, we found that MZB1 was preferentially enriched in the pool of citrullinated lung proteins obtained from patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) compared to those from idiopathic pulmonary fibrosis or chronic obstructive pulmonary diseases. The citrullination of MZB1 was confirmed with mass spectrometry, in vitro citrullination, and binding by phenylglyoxal in the absence or presence of a PAD2-specific inhibitor AFM-30a. Ablation or pharmacological inhibition of PAD2 in primary human B cells attenuated the secretion of IgM and IgA but not IgG or the differentiation of IgM or IgA-expressing plasmablasts, recapitulating the effect of ablating MZB1. In addition, the physical interaction between endogenous MZB1 and IgM/IgA was attenuated by AFM-30a. Taken together, our data confirm the function of MZB1 in primary human plasmablasts and suggest that PAD2 promotes IgM/IgA secretion by citrullinating MZB1, thereby contributing to the pathogenesis of rheumatoid arthritis and RA-ILD.
2023-11-23 | PXD047044 | Pride
Project description:Majority of B cell malignancies originate in the germinal centers (GCs), where B cells undergo activation to mutationally diversify their antibody genes and switch from the default Immunoglobulin M (IgM) or IgD B cell receptor (BCR) to IgG, IgA or IgE BCR isotypes. Similar to normal B cells, malignant B cells rely on signals emanating from the BCR for their survival and growth. While studies have primarily focused on elucidating the functions of IgM-mediated signaling in lymphoma pathogenesis, GC-derived lymphomas also express IgG and IgA BCR isotypes that greatly differ from IgM in their signaling potential. How these distinct non-IgM BCRs contribute to the pathogenesis of B cell malignancies is not well understood. Interestingly, B cell lymphoma patients expressing IgG BCR isotypes show better prognosis and survival than those expressing IgM BCR isotype. Consistent with this, we show that Diffuse Large B Cell Lymphoma (DLBCL) patients with higher IgG1 expression are associated with lower stages of disease than those with higher IgM expression. To directly test the roles of distinct BCR isotypes, we developed isogenic lymphoma cells that either express IgM or IgG1 BCRs. Interestingly, the IgG1-switched lymphoma cells fail to form tumors in mice whereas their IgM counterparts establish aggressive tumors. Moreover, co-transplantation of IgG1 and IgM expressing human and mouse lymphoma cells leads to emergence of tumors expressing IgM (and not IgG1), demonstrating that IgM BCRs are strongly favored over IgG1. Mechanistically, IgG1 expressing lymphoma cells and non-malignant activated B cells have reduced survival which is associated with a dysfunctional mitochondrial state triggered by stronger calcium responses in IgG1 in comparison to IgM cells. Genetic reversal of IgG1 to IgM or pharmacological dampening of the calcium signaling is sufficient to correct the mitochondrial defects and rescue the survival of IgG1 B cells. Our findings demonstrate that distinct BCR isotypes are inherently unique in their activities and can differentially impact B cell lymphoma pathogenesis.
2025-04-18 | GSE249885 | GEO
Project description:IgG cytoplasmic tail interferes with the induction of antigen-response genes Experiment Overall Design: Comparing antigen-induced genes between B cells expressing anti-HEL IgM BCR and IgMG BCR (chimeric receptor where the extracellular spacer, transmembrane, and cytoplasmic domain of IgM are replaced with those of IgG1)
2008-06-15 | E-GEOD-7218 | biostudies-arrayexpress
Project description:Although N-linked glycans play pivotal roles in the regulation of antibody effector functions, little is known about the composition and functional impact of glycans expressed by human B cell receptors (BCRs), likely due to technical challenges. Here, we describe the site-specific glycosylation profiles of all four N-linked glycosylation-sites of human IgM BCRs from primary naive and memory B cells. We show that the BCR glycans have not undergone structural changes during the transition from naive to memory cells. Moreover, using B cell lines expressing well-defined BCRs, we show that individual glycosylation sites are non-essential for cell-surface expression, and that the absence of the IgM BCR N209 glycan reduces the antigen-binding capacity of B cells. Collectively, these findings shows high conservation of IgM BCR glycosylation across IgM BCR B cell subsets and indicate a limited contribution to BCR expression and function, suggesting BCR glycans may have evolved to support IgM antibody functions.
2025-12-09 | PXD062559 | Pride
Project description:Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense. Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype specific gene regulation are largely unaddressed. Here, we performed ATAC-seq on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection. We observed isotype-specific chromatin accessibility patterns that indicate distinct functions underpin ASC of each isotype.
2026-07-30 | GSE314193 | GEO
Project description:Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense. Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype specific gene regulation are largely unaddressed. Here, we performed RNA-seq on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection. We observed isotype-specific expression patterns that indicate distinct functions underpin ASC of each isotype.
2026-07-30 | GSE314192 | GEO
Project description:Antibody-secreting cells (ASCs) are critical effectors of humoral immunity, wherein their distinct isotypes play specialized roles in pathogen defense. Despite studies defining the transcriptional programs of selected ASC isotypes, specific mechanisms underlying isotype specific gene regulation are largely unaddressed. Here, we performed Reduced Representation Bisulfite Sequencing (RRBS) on surface-sorted IgM, IgG, and IgA ASCs isolated from the spleens and mediastinal lymph nodes of mice following influenza infection. We observed isotype-specific DNA methylation patterns that indicate distinct functions underpin ASC of each isotype.
2026-07-30 | GSE314196 | GEO
Project description:c-myc-3'RR mice developed Burkitt like lymphoma (IgM and IgD positive cells). We wished to study lymphomagenesis in mice carrying a modified B cell receptor with a higher level of tonic signal. The c-myc-3'RR transgene was introduced in a background with an IgH mutation that replaces IgM with IgA expression. Lymphoma arising in double mutant animals mostly carried the phenotype of activated cells, often expressing CD43, and in 10% of cases carrying a plasma cell phenotype. BCR tonic signal appears as a direct modulator of B cell malignancy phenotype. Burkitt lymphoma (BL) from 4 c-myc-3'RR mice, anaplastic (ANA) lymphoma from 4 c-myc-3'RR mice, CD43 negative lymphoma from 4 c-myc-IgA mice and CD43 positive lymphoma from 4 c-myc-IgA mice were investigated.
2012-02-01 | E-GEOD-32229 | biostudies-arrayexpress
Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with Anti-IgM labeled with Cy5- time course with repeats Keywords: ordered
2003-04-14 | GSE371 | GEO
Project description:IgM monoclonal gammopathy of undetermined significance (IgM MGUS) is an early precursor stage of the rare lymphoma Waldenström Macroglobulinemia (WM). Although comparative gene expression studies on WM, IgM MGUS, and normal B cells identified several genes differently expressed, reliable predictors of progression from IgM MGUS to WM have not yet been identified. We performed a microarray study on CD19+ and CD138+ cells of WM vs. IgM MGUS vs. CTRLs to determine gene signatures for both cell populations. We demonstrated that hematopoietic antigens, cell-adhesion molecules, Wnt signaling, BCR signaling, calcium signaling, coagulation cascade, and pathways responsible for cell cycle and proliferation were significantly enriched for genes expressed in B cells of WM vs. IgM MGUS vs. CTRLs. Notably, we showed nine genes which displayed the same expression levels in both WM and IgM MGUS compared to CTRLs, suggesting their possible role in the risk of transformation in IgM MGUS to WM.
2021-04-09 | GSE171739 | GEO