The microRNA processing subunit DGCR8 is required for a T cell-dependent germinal center response

Front Immunol. 2022 Dec 16:13:991347. doi: 10.3389/fimmu.2022.991347. eCollection 2022.

Abstract

We have previously shown that the microRNA (miRNA) processor complex consisting of the RNAse Drosha and the DiGeorge Critical Region (DGCR) 8 protein is essential for B cell maturation. To determine whether miRNA processing is required to initiate T cell-mediated antibody responses, we deleted DGCR8 in maturing B2 cells by crossing a mouse with loxP-flanked DGCR8 alleles with a CD23-Cre mouse. As expected, non-immunized mice showed reduced numbers of mature B2 cells and IgG-secreting cells and diminished serum IgG titers. In accordance, germinal centers and antigen-specific IgG-secreting cells were absent in mice immunized with T-dependent antigens. Therefore, DGCR8 is required to mount an efficient T-dependent antibody response. However, DGCR8 deletion in B1 cells was incomplete, resulting in unaltered B1 cell numbers and normal IgM and IgA titers in DGCR8-knock-out mice. Therefore, this mouse model could be used to analyze B1 responses in the absence of functional B2 cells.

Keywords: B1 cell; DGCR8; DiGeorge syndrome critical region 8 protein; antibody-secreting cell; germinal center response; microRNA; plasma cell (PC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Germinal Center / metabolism
  • Immunoglobulin G / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • T-Lymphocytes / metabolism

Substances

  • MicroRNAs
  • RNA-Binding Proteins
  • Immunoglobulin G
  • Dgcr8 protein, mouse