MicroRNA Fine-Tuning of the Germinal Center Response.

Teresa Fuertes,Irene Salgado,Virginia G De Yébenes

doi:10.3389/fimmu.2021.660450

Abstract

Germinal centers (GCs) are complex multicellular structures in which antigen-specific B cells undergo the molecular remodeling that enables the generation of high-affinity antibodies and the differentiation programs that lead to the generation of plasma–antibody-secreting cells and memory B cells. These reactions are tightly controlled by a variety of mechanisms, including the post-transcriptional control of gene expression by microRNAs (miRNAs). Through the development of animal models with B cell-specific modified miRNA expression, we have contributed to the understanding of the role of miRNAs in the regulation of GC responses and in B cell neoplasia. Here, we review recent advances in the understanding of the role of miRNAs in the regulation of B cell and T follicular helper physiology during the GC response and in the diseases associated to GC response dysregulation.

Highlights

The germinal center (GC) response is a key B lymphocyte maturation and differentiation program essential for the generation of competent protective immunity
The miR-17-92 polycistron, which promotes GC responses by enhancing Tfh and B lymphocyte proliferation and survival by inhibiting the expression of Pten and Bim [10, 48, 49, 51], when overexpressed in different mouse models promotes the generation of spontaneous GCs, IgG anti-double–stranded DNA autoantibodies linked to fatal immunopathology [48, 51], and B cell GC-derived lymphoma [50]
Studies by many groups in the field have shown that miRNAs play a key role in GC-response regulation and are required to prevent GCderived autoimmunity and B cell neoplasia

Summary

Introduction

The germinal center (GC) response is a key B lymphocyte maturation and differentiation program essential for the generation of competent protective immunity. T cell-specific miR-17-92 gain- and loss-of function mouse models showed that the microRNAs of the cluster are critical promoters of Tfh and GC B cell differentiation and antigen-specific antibody generation during both T-cell dependent immune responses and chronic viral infection [10, 48, 49].

Results

Conclusion