Presentation Title
The Role of Glycogen Metabolism in B Cell Effector Function
Abstract
Upon activation, B cells increase their metabolic activity and have an increased demand for glucose. In the event that glucose is depleted, another source of energy must become available to meet the metabolic needs required for various effector functions including proliferation, antibody-secretion, and class-switching. We have previously shown that dendritic cells store glycogen for early effector cell activation. Here, we show that B-cells also express the enzymatic machinery required for glycogen metabolism. These include the two rate-limiting enzymes required for the synthesis and breakdown of glycogen, glycogen synthase (GYS) and glycogen phosphorylase (PYG), respectively. Upon chemical inhibition of PYG with CP-91149, we observed a decrease in both cell proliferation and antibody secretion. However, this dose of CP-91149 did not impact overall cell survival, therefore indicating that inhibition of PYG alone negatively impacted downstream effector functions of B-cells. In the future, we will be comparing the effects of GYS1 knockdown in B-cells using murine models to PYG pharmacological inhibition.
Primary Faculty Mentor Name
Eyal Amiel
Graduate Student Mentors
Princess Rodriguez
Faculty/Staff Collaborators
Princess Rodriguez
Status
Undergraduate
Student College
College of Agriculture and Life Sciences
Program/Major
Biochemistry
Primary Research Category
Biological Sciences
Secondary Research Category
Health Sciences
The Role of Glycogen Metabolism in B Cell Effector Function
Upon activation, B cells increase their metabolic activity and have an increased demand for glucose. In the event that glucose is depleted, another source of energy must become available to meet the metabolic needs required for various effector functions including proliferation, antibody-secretion, and class-switching. We have previously shown that dendritic cells store glycogen for early effector cell activation. Here, we show that B-cells also express the enzymatic machinery required for glycogen metabolism. These include the two rate-limiting enzymes required for the synthesis and breakdown of glycogen, glycogen synthase (GYS) and glycogen phosphorylase (PYG), respectively. Upon chemical inhibition of PYG with CP-91149, we observed a decrease in both cell proliferation and antibody secretion. However, this dose of CP-91149 did not impact overall cell survival, therefore indicating that inhibition of PYG alone negatively impacted downstream effector functions of B-cells. In the future, we will be comparing the effects of GYS1 knockdown in B-cells using murine models to PYG pharmacological inhibition.