Frontiers in Immunology (Dec 2022)

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

  • Patrick Daum,
  • Shannon R. Ottmann,
  • Julia Meinzinger,
  • Sebastian R. Schulz,
  • Joana Côrte-Real,
  • Manuela Hauke,
  • Edith Roth,
  • Wolfgang Schuh,
  • Dirk Mielenz,
  • Hans-Martin Jäck,
  • Katharina Pracht

DOI
https://doi.org/10.3389/fimmu.2022.991347
Journal volume & issue
Vol. 13

Abstract

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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.

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