Deletion of Mettl3 at the Pro-B Stage Marginally Affects B Cell Development and Profibrogenic Activity of B Cells in Liver Fibrosis.

Citation metadata

Date: June 14, 2022
Publisher: Hindawi Limited
Document Type: Article
Length: 9,451 words
Lexile Measure: 1470L

Document controls

Main content

Abstract :

N6-methyladenosine (m[sup.6]A) modification plays a pivotal role in cell fate determination. Previous studies show that eliminating m[sup.6]A using Mb1-Cre dramatically impairs B cell development. However, whether disturbing m[sup.6]A modification at later stages affects B cell development and function remains elusive. Here, we deleted m[sup.6]A methyltransferase Mettl3 from the pro-B stage on using Cd19-Cre (Mettl3 cKO) and found that the frequency of total B cells in peripheral blood, peritoneal cavity, and liver is comparable between Mettl3 cKO mice and wild-type (WT) littermates, while the percentage of whole splenic B cells slightly increases in Mettl3 cKO individuals. The proportion of pre-pro-B, pro-B, pre-B, immature, and mature B cells in the bone marrow were minimally affected. Loss of Mettl3 resulted in increased apoptosis but barely affected B cells' proliferation and IgG production upon LPS, CD40L, anti-IgM, or TNF-α stimulation. Different stimuli had different effects on B cell activation. In addition, B cell-specific Mettl3 knockout had no influence on the pro-fibrogenic activity of B cells in liver fibrosis, evidenced by comparable fibrosis in carbon tetrachloride- (CCl[sub.4]-) treated Mettl3 cKO mice and WT controls. In summary, our study demonstrated that deletion of Mettl3 from the pro-B stage on has minimal effects on B cell development and function, as well as profibrogenic activity of B cells in liver fibrosis, revealing a stage-specific dependence on Mettl3-mediated m[sup.6]A of B cell development.

Source Citation

Source Citation   

Gale Document Number: GALE|A708347139