Biology subjects

Jäck, H.-M.

Publications and source records attributed to Jäck, H.-M..

2 recordsLinked to original sources

bioRxiv2022

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

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.

immunology↗

bioRxiv2021

The Omicron variant is highly resistant against antibody-mediated neutralization - implications for control of the COVID-19 pandemic

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

microbiology↗