2.50
Hdl Handle:
http://hdl.handle.net/10033/596960
Title:
MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis.
Authors:
Nakagawa, Rinako; Leyland, Rebecca; Meyer-Hermann, Michael ( 0000-0002-4300-2474 ) ; Lu, Dong; Turner, Martin; Arbore, Giuseppina; Phan, Tri Giang; Brink, Robert; Vigorito, Elena
Abstract:
The production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood. Here, we utilized a miR-155 reporter mouse strain and showed that miR-155 is coexpressed with the proto-oncogene encoding c-MYC in positively selected B cells. Functionally, miR-155 protected positively selected c-MYC+ B cells from apoptosis, allowing clonal expansion of this population, providing an explanation as to why Mir155 deletion impairs affinity maturation and promotes the premature collapse of GCs. We determined that miR-155 directly inhibits the Jumonji family member JARID2, which enhances B cell apoptosis when overexpressed, and thereby promotes GC B cell survival. Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
MicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis. 2016, 126 (1):377-88 J. Clin. Invest.
Journal:
The Journal of clinical investigation
Issue Date:
4-Jan-2016
URI:
http://hdl.handle.net/10033/596960
DOI:
10.1172/JCI82914
PubMed ID:
26657861
Type:
Article
Language:
en
ISSN:
1558-8238
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorNakagawa, Rinakoen
dc.contributor.authorLeyland, Rebeccaen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.contributor.authorLu, Dongen
dc.contributor.authorTurner, Martinen
dc.contributor.authorArbore, Giuseppinaen
dc.contributor.authorPhan, Tri Giangen
dc.contributor.authorBrink, Roberten
dc.contributor.authorVigorito, Elenaen
dc.date.accessioned2016-02-23T10:50:23Zen
dc.date.available2016-02-23T10:50:23Zen
dc.date.issued2016-01-04en
dc.identifier.citationMicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis. 2016, 126 (1):377-88 J. Clin. Invest.en
dc.identifier.issn1558-8238en
dc.identifier.pmid26657861en
dc.identifier.doi10.1172/JCI82914en
dc.identifier.urihttp://hdl.handle.net/10033/596960en
dc.description.abstractThe production of high-affinity antibodies by B cells is essential for pathogen clearance. Antibody affinity for antigen is increased through the affinity maturation in germinal centers (GCs). This is an iterative process in which B cells cycle between proliferation coupled with the acquisition of mutations and antigen-based positive selection, resulting in retention of the highest-affinity B cell clones. The posttranscriptional regulator microRNA-155 (miR-155) is critical for efficient affinity maturation and the maintenance of the GCs; however, the cellular and molecular mechanism by which miR-155 regulates GC responses is not well understood. Here, we utilized a miR-155 reporter mouse strain and showed that miR-155 is coexpressed with the proto-oncogene encoding c-MYC in positively selected B cells. Functionally, miR-155 protected positively selected c-MYC+ B cells from apoptosis, allowing clonal expansion of this population, providing an explanation as to why Mir155 deletion impairs affinity maturation and promotes the premature collapse of GCs. We determined that miR-155 directly inhibits the Jumonji family member JARID2, which enhances B cell apoptosis when overexpressed, and thereby promotes GC B cell survival. Our findings also suggest that there is cooperation between c-MYC and miR-155 during the normal GC response, a cooperation that may explain how c-MYC and miR-155 can collaboratively function as oncogenes.en
dc.language.isoenen
dc.titleMicroRNA-155 controls affinity-based selection by protecting c-MYC+ B cells from apoptosis.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalThe Journal of clinical investigationen

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