4.7 Article

Protein arginine methyltransferase 1 regulates B cell fate after positive selection in the germinal center in mice

Journal

JOURNAL OF EXPERIMENTAL MEDICINE
Volume 220, Issue 9, Pages -

Publisher

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20220381

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Protein arginine methyltransferase 1 (PRMT1) is upregulated via Myc and mTORC1 during positive selection and plays a critical role in transcription. Deleting Prmt1 compromises antibody affinity maturation by hampering proliferation and cycling of GCBC. Moreover, Prmt1 restricts plasma cell differentiation and this function is co-opted by B cell lymphoma cells.
Positively selected germinal center B cells (GCBC) can either resume proliferation and somatic hypermutation or differentiate. The mechanisms dictating these alternative cell fates are incompletely understood. We show that the protein arginine methyltransferase 1 (Prmt1) is upregulated in murine GCBC by Myc and mTORC-dependent signaling after positive selection. Deleting Prmt1 in activated B cells compromises antibody affinity maturation by hampering proliferation and GCBC light zone to dark zone cycling. Prmt1 deficiency also results in enhanced memory B cell generation and plasma cell differentiation, albeit the quality of these cells is compromised by the GCBC defects. We further demonstrate that Prmt1 intrinsically limits plasma cell differentiation, a function co-opted by B cell lymphoma (BCL) cells. Consistently, PRMT1 expression in BCL correlates with poor disease outcome, depends on MYC and mTORC1 activity, is required for cell proliferation, and prevents differentiation. Collectively, these data identify PRMT1 as a determinant of normal and cancerous mature B cell proliferation and differentiation balance. Protein arginine methyltransferase 1 (PRMT1) is upregulated via Myc and mTORC1 during positive selection and influences germinal center B cell fate. PRMT1 promotes antibody affinity maturation by favoring dark zone fate and proliferation while limiting differentiation, two functions that are co-opted by mature B cell lymphoma cells.

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