Selenoproteins regulate B cell development and peripheral homeostasis
Restricted (Penn State Only)
- Author:
- Sumner, Sarah Elizabeth
- Graduate Program:
- Pathobiology
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- April 13, 2022
- Committee Members:
- Girish Kirimanjeswara, Chair & Dissertation Advisor
Margherita Cantorna, Major Field Member
Santhosh Girirajan, Outside Unit & Field Member
Troy Sutton, Major Field Member
Kumble Prabhu, Major Field Member
Kumble Prabhu, Program Head/Chair - Keywords:
- B lymphocyte
B cell
Selenoproteins
Selenium
SelenoW
SelenoH
B cell Development
Reactive Oxygen Species
ROS
NAC - Abstract:
- Selenium, which exerts its biological effects via selenoproteins, has been shown to be required for optimal functioning of the immune system. However, few studies have investigated the role of selenoproteins during B cell development and peripheral homeostasis. In the first study, we show that B cell selenoprotein deficiency results in a decrease in the number of B220+ splenocytes including follicular, marginal zone, and germinal center B cells which correlates to a reduction in the amount of circulating serum immunoglobulins. This results in severe immunological defects following a vaccination and challenge model. The B cell defects observed following deletion of B cell-specific selenoproteins are due to an inability to control reactive oxygen species (ROS) leading to an increase in cell death following stimulation. The second study demonstrates that B cell selenoprotein deficiency results in a B cell developmental defect which occurs following the large to small pre-B cell transition. This developmental defect may be restored to that of control numbers by the addition of N-acetylcysteine (an ROS scavenger), suggesting a role for uncontrolled ROS during B cell development in the absence of selenoproteins. RNAseq data of pre-B cells reveal a potential role for selenoW and selenoH during this developmental transition. We propose a role for selenoW as a negative regulator of B cell development and speculate that selenoH may function as the positive regulator. The third study demonstrates a developmental defect in innate like B1 cells that occurs during the first wave of B1 cell development in utero. These data indicate a previously uncharacterized role for selenoproteins in the development and maintenance of both conventional B2 and innate-like B1 lymphocytes.