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

  • Nat Immunol. 2018 Mar;19(3):267-278. doi: 10.1038/s41590-017-0035-5.
Elisa Monzón-Casanova  1  2 ,  Michael Screen  1 ,  Manuel D Díaz-Muñoz  1 ,  Richard M R Coulson  1 ,  Sarah E Bell  1 ,  Greta Lamers  1 ,  Michele Solimena  3  4  5  6 ,  Christopher W J Smith  2 ,  Martin Turner  7
Affiliations
  • 1. Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, UK.
  • 2. Department of Biochemistry, University of Cambridge, Cambridge, UK.
  • 3. Molecular Diabetology, University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
  • 4. Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
  • 5. Max Planck Institute for Molecular Cell Biology and Genetics, Dresden, Germany.
  • 6. German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  • 7. Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, UK. [email protected].
PMID: 29358707 DOI: 10.1038/s41590-017-0035-5
Abstract

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.

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