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 central B cell maturation. To determine whether miRNA processing is required to initiate T cell-mediated antibody responses, we deleted DGCR8 in maturing B-2 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 B-2 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 cell-dependent antigens. Therefore, DGCR8 is required to mount an efficient T cell-dependent antibody response. However, DGCR8 deletion in B-1 cells was incomplete, which explains relatively unaffected B-1 cell numbers and adequate IgM and IgA titers in DGCR8-knock out mice and suggests that this mouse model could be used to analyze B-1 responses in the absence of functional B-2 cells.
Competing Interest Statement
The authors have declared no competing interest.
ABBREVIATIONS
- ASC=
- antibody-secreting cell;
- BCR=
- B cell receptor;
- BM=
- bone marrow;
- DGCR8
- DiGeorge Critical Region 8;
- FO=
- follicular;
- GC=
- germinal center;
- Ig=
- immunoglobulin;
- miRNA=
- microRNA;
- MZ=
- marginal zone;
- PI=
- propidium iodide;
- RISC=
- RNA induced silencing complex;
- SRBC=
- sheep red blood cells;
- TD=
- thymus-dependent;
- TNP-KLH=
- 2,4,6-Trinitrophenyl Keyhole Limpet Hemocyanin.