Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Protein Amounts of the MYC Transcription Factor Determine Germinal Center B Cell Division Capacity.

ABSTRACT: High-affinity B cell selection in the germinal center (GC) is governed by signals delivered by follicular helper T (Tfh) cells to B cells. Selected B cells undergo clonal expansion and affinity maturation in the GC dark zone in direct proportion to the amount of antigen they capture and present to Tfh cells in the light zone. Here, we examined the mechanisms whereby Tfh cells program the number of GC B cell divisions. Gene expression analysis revealed that Tfh cells induce Myc expression in light-zone B cells in direct proportion to antigen capture. Conditional Myc haplo-insufficiency or overexpression combined with cell division tracking showed that MYC expression produces a metabolic reservoir in selected light-zone B cells that is proportional to the number of cell divisions in the dark zone. Thus, MYC constitutes the GC B cell division timer that when deregulated leads to emergence of B cell lymphoma.

SUBMITTER: Finkin S

PROVIDER: S-EPMC6703930 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Protein Amounts of the MYC Transcription Factor Determine Germinal Center B Cell Division Capacity.

Finkin Shlomo S Hartweger Harald H Oliveira Thiago Y TY Kara Ervin E EE Nussenzweig Michel C MC

Immunity 20190723 2

High-affinity B cell selection in the germinal center (GC) is governed by signals delivered by follicular helper T (Tfh) cells to B cells. Selected B cells undergo clonal expansion and affinity maturation in the GC dark zone in direct proportion to the amount of antigen they capture and present to Tfh cells in the light zone. Here, we examined the mechanisms whereby Tfh cells program the number of GC B cell divisions. Gene expression analysis revealed that Tfh cells induce Myc expression in ligh ...[more]

PMID: 31350178

Similar Datasets

Protein amounts of the MYC transcription factor determine germinal center B cell division capacity

Project description:High affinity B cell selection in the germinal center (GC) is governed by signals delivered by follicular helper T cells (Tfh) to B cells. Selected B cells undergo clonal expansion and affinity maturation in the GC dark zone in direct proportion to the amount of antigen they capture and present to Tfh cells in the light zone. Here we examined the mechanisms whereby Tfh cells program the number of GC B cell divisions. Gene expression analysis revealed that Tfh induce MYC expression in light zone B cells in direct proportion to antigen capture. Conditional Myc haplo-insufficiency or over-expression combined with cell division tracking showed that MYC expression produces a metabolic reservoir in selected light zone B cells that is proportional to the number of cell divisions in the dark zone. Thus, MYC constitutes the germinal center B cell division timer that when deregulated leads to emergence of B cell lymphoma.

2019-06-18 | GSE132881 | GEO

Protein amounts of the MYC transcription factor determine germinal center B cell division capacity

Project description:Protein amounts of the MYC transcription factor determine germinal center B cell division capacity

| PRJNA549338 | ENA

MYC-MIZ1 protein interaction in germinal center.

Project description:Characterisation of the splenic light zone germinal center B cells in mice carrying WT endogenous mouse allele and mice carrying a mouse allele (Myc V394D) unable to bind its partner transcription factor Miz1 (Zbtb17). Characterisation of Myc WT memory B cells.

2020-05-08 | GSE129262 | GEO

Asymmetric B cell division in the germinal center reaction.

Project description:Lifelong antibody responses to vaccination require reorganization of lymphoid tissue and dynamic intercellular communication called the germinal center reaction. B lymphocytes undergo cellular polarization during antigen stimulation, acquisition, and presentation, which are critical steps for initiating humoral immunity. Here, we show that germinal center B lymphocytes asymmetrically segregate the transcriptional regulator Bcl6, the receptor for interleukin-21, and the ancestral polarity protein atypical protein kinase C to one side of the plane of division, generating unequal inheritance of fate-altering molecules by daughter cells. Germinal center B lymphocytes from mice with a defect in leukocyte adhesion fail to divide asymmetrically. These results suggest that motile cells lacking constitutive attachment can receive provisional polarity cues from the microenvironment to generate daughter cell diversity and self-renewal.

| S-EPMC3282111 | biostudies-literature

B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells.

Project description:Positive selection of germinal center (GC) B cells is driven by B cell receptor (BCR) affinity and requires help from follicular T helper cells. The transcription factors c-Myc and Foxo1 are critical for GC B cell selection and survival. However, how different affinity-related signaling events control these transcription factors in a manner that links to selection is unknown. Here we showed that GC B cells reprogram CD40 and BCR signaling to transduce via NF-?B and Foxo1, respectively, whereas naive B cells propagate both signals downstream of either receptor. Although either BCR or CD40 ligation induced c-Myc in naive B cells, both signals were required to highly induce c-Myc, a critical mediator of GC B cell survival and cell cycle reentry. Thus, GC B cells rewire their signaling to enhance selection stringency via a requirement for both antigen receptor- and T cell-mediated signals to induce mediators of positive selection.

| S-EPMC5821563 | biostudies-literature

MYC-MIZ1 protein interaction in germinal center.

Project description:MYC-MIZ1 protein interaction in germinal center.

| PRJNA530681 | ENA

Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation.

Project description:Follicular T-helper (T(FH)) cells cooperate with GL7(+)CD95(+) germinal center (GC) B cells to induce antibody maturation. Herein, we identify the transcription factor IRF4 as a T-cell intrinsic precondition for T(FH) cell differentiation and GC formation. After immunization with protein or infection with the protozoon Leishmania major, draining lymph nodes (LNs) of IFN-regulatory factor-4 (Irf4(-/-)) mice lacked GCs and GC B cells despite developing normal initial hyperplasia. GCs were also absent in Peyer's patches of naive Irf4(-/-) mice. Accordingly, CD4(+) T cells within the LNs and Peyer's patches failed to express the T(FH) key transcription factor B-cell lymphoma-6 and other T(FH)-related molecules. During chronic leishmaniasis, the draining Irf4(-/-) LNs disappeared because of massive cell death. Adoptive transfer of WT CD4(+) T cells or few L. major primed WT T(FH) cells reconstituted GC formation, GC B-cell differentiation, and LN cell survival. In support of a T-cell intrinsic IRF4 activity, Irf4(-/-) T(FH) cell differentiation was not rescued by close neighborhood to transferred WT T(FH) cells. Together with its known B lineage-specific roles during plasma cell maturation and class switch, our study places IRF4 in the center of antibody production toward T-cell-dependent antigens.

| S-EPMC3365194 | biostudies-literature

Transcription factor Phf19 positively regulates germinal center reactions that underlies its role in rheumatoid arthritis.

Project description:The Polycomb Repressive Complex 2 (PRC2) component PHD Finger Protein 19 (phf19) gene has been identified to be associated with rheumatoid arthritis (RA) risk. Here we show that Phf19 is highly expressed in murine germinal centers (GCs) and RA patients. To investigate the function of Phf19 in lymphocytes, we generated RAG1-deficient mice reconstituted with Phf19 or control-vector transduced bone marrow (BM) cells. Lymphogenesis in primary lymphoid tissues of Phf19-RM is normal, however, Phf19-RM form enlarged GCs and generate more antibody-secreting cells (ASCs). Overexpression of Phf19 promotes proliferation and survival of GC B cells and Tfh cells in vivo. The uncovered Phf19-dependent targets include the genes encoding cyclin D2, the prosurvival factor Bcl-xL and CD40-CD40 ligand axis, their regulation by Phf19 could partially elucidate the advantages observed in Phf19-overexpressing GCs. Our results underscore an unrecognized but critical function for Phf19 in GCs formation and antibody generation, and implicate the potential role of Phf19 in RA pathogenesis.

| S-EPMC5801358 | biostudies-literature

The LRF transcription factor regulates mature B cell development and the germinal center response in mice.

Project description:B cells play a central role in immune system function. Deregulation of normal B cell maturation can lead to the development of autoimmune syndromes as well as B cell malignancies. Elucidation of the molecular features of normal B cell development is important for the development of new target therapies for autoimmune diseases and B cell malignancies. Employing B cell-specific conditional knockout mice, we have demonstrated here that the transcription factor leukemia/lymphoma-related factor (LRF) forms an obligate dimer in B cells and regulates mature B cell lineage fate and humoral immune responses via distinctive mechanisms. Moreover, LRF inactivation in transformed B cells attenuated their growth rate. These studies identify what we believe to be a new key factor for mature B cell development and provide a rationale for targeting LRF dimers for the treatment of autoimmune diseases and B cell malignancies.

| S-EPMC3223838 | biostudies-literature

The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.

Project description:Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture, which is consistent with recent studies. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch.

| S-EPMC5379976 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data