Postmitotic G1 phase survivin drives mitogen-independent cell division of B lymphocytes

Author:

Singh Amit1ORCID,Spitzer Matthew H.2,Joy Jaimy P.1,Kaileh Mary1,Qiu Xiang1ORCID,Nolan Garry P.2,Sen Ranjan1

Affiliation:

1. Gene Regulation Section, Laboratory of Molecular Biology and Immunology, National Institute on Aging, Baltimore, MD 21224

2. Department of Microbiology and Immunology, Baxter Laboratory of Stem Cell Biology, Stanford University, School of Medicine, Stanford, CA 94305

Abstract

Significance The prevailing dogma is that renewed mitogenic signaling is essential to traverse G1 phase of the cell cycle after each division. B lymphocytes undergo multiple mitotic divisions, termed clonal expansion, to expand antigen-specific cells that mediate effective immunity. Here we demonstrate that B cells that have undergone one cell division continue to proliferate even in absence of further mitogenic signals. This mitogen-independent proliferation is accompanied by an altered G1 phase marked by transcriptomic and proteomic features of G2/M. Survivin, a G2/M-specific oncogene, is required in G1 to achieve mitogen-independent proliferation.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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