The RNA-binding protein PTBP1 is necessary for B cell selection in germinal centers

Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid pro...

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Veröffentlicht in:Nature immunology 2018-03, Vol.19 (3), p.267-278
Hauptverfasser: Monzón-Casanova, Elisa, Screen, Michael, Díaz-Muñoz, Manuel D., Coulson, Richard M. R., Bell, Sarah E., Lamers, Greta, Solimena, Michele, Smith, Christopher W. J., Turner, Martin
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Sprache:eng
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Zusammenfassung:Antibody affinity maturation occurs in germinal centers (GCs), where B cells cycle between the light zone (LZ) and the dark zone. In the LZ, GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from helper T cells, which promotes their rapid proliferation. Here we found that the RNA-binding protein PTBP1 was needed for the progression of GC B cells through late S phase of the cell cycle and for affinity maturation. PTBP1 was required for proper expression of the c-MYC-dependent gene program induced in GC B cells receiving T cell help and directly regulated the alternative splicing and abundance of transcripts that are increased during positive selection to promote proliferation. Affinity maturation and positive selection occur in germinal centers. Turner and colleagues demonstrate that the RNA-binding protein PTBP1 serves an essential B cell–intrinsic role by regulating the abundance and alternate splicing of transcripts in germinal center B cells.
ISSN:1529-2908
1529-2916
DOI:10.1038/s41590-017-0035-5