Lamin B1 regulates somatic mutations and progression of B-cell malignancies

20Citations
Citations of this article
53Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Somatic hypermutation (SHM) is a pivotal process in adaptive immunity that occurs in the germinal centre and allows B cells to change their primary DNA sequence and diversify their antigen receptors. Here, we report that genome binding of Lamin B1, a component of the nuclear envelope involved in epigenetic chromatin regulation, is reduced during B-cell activation and formation of lymphoid germinal centres. Chromatin immunoprecipitation-Seq analysis showed that kappa and heavy variable immunoglobulin domains were released from the Lamin B1 suppressive environment when SHM was induced in B cells. RNA interference-mediated reduction of Lamin B1 resulted in spontaneous SHM as well as kappa-light chain aberrant surface expression. Finally, Lamin B1 expression level correlated with progression-free and overall survival in chronic lymphocytic leukaemia, and was strongly involved in the transformation of follicular lymphoma. In summary, here we report that Lamin B1 is a negative epigenetic regulator of SHM in normal B-cells and a 'mutational gatekeeper', suppressing the aberrant mutations that drive lymphoid malignancy.

Cite

CITATION STYLE

APA

Klymenko, T., Bloehdorn, J., Bahlo, J., Robrecht, S., Akylzhanova, G., Cox, K., … Braun, A. (2018). Lamin B1 regulates somatic mutations and progression of B-cell malignancies. Leukemia, 32(2), 364–375. https://doi.org/10.1038/leu.2017.255

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free