The MiR-155-PU.1 Axis Acts on Pax5 to Enable Efficient Terminal B Cell Differentiation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2014 Oct 8

PMID 25288398

Citations 49

Authors

Dong Lu

Rinako Nakagawa

Sandra Lazzaro

Philipp Staudacher

Cei Abreu-Goodger

Tom Henley

Sara Boiani

Rebecca Leyland

Alison Galloway

Simon Andrews

Geoffrey Butcher

Stephen L Nutt

Martin Turner

Elena Vigorito

Affiliations

Soon will be listed here.

Abstract

A single microRNA (miRNA) can regulate the expression of many genes, though the level of repression imparted on any given target is generally low. How then is the selective pressure for a single miRNA/target interaction maintained across long evolutionary distances? We addressed this problem by disrupting in vivo the interaction between miR-155 and PU.1 in mice. Remarkably, this interaction proved to be key to promoting optimal T cell-dependent B cell responses, a previously unrecognized role for PU.1. Mechanistically, miR-155 inhibits PU.1 expression, leading to Pax5 down-regulation and the initiation of the plasma cell differentiation pathway. Additional PU.1 targets include a network of genes whose products are involved in adhesion, with direct links to B-T cell interactions. We conclude that the evolutionary adaptive selection of the miR-155-PU.1 interaction is exercised through the effectiveness of terminal B cell differentiation.

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