Retinoic Acid and alpha-galactosylceramide Regulate Antigen Presenting Cell Functions

Open Access
Author:
Liu, Jason R
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • A Catharine Ross, Thesis Supervisor
  • Stephen Wade Schaeffer, Honors Advisor
Keywords:
  • retinoic acid
  • RA
  • alpha-galactosylceramide
  • aGalCer
  • CD1d
  • antigen presenting cells
  • APCs
  • monocytes
  • B cells
Abstract:
Antigen presenting cells (APCs)―particularly macrophages, dendritic cells, and B cells―play an important role in the immune system. APCs augment the immune response by activating T cells through major histocompatibility complex (MHC) class II molecules present on the APC cell surface. APCs also augment the immune response by activating invariant natural killer T (iNKT) cells through CD1d, an MHC class-I-like molecule present on the surface of certain APCs that presents lipid antigens. The focus of this thesis will be on the regulation of CD1d expression in APCs and the activation of B cells through CD1d after the addition of all-trans retinoic acid (RA) and α-galactosylceramide (αGalCer). Previously, it was reported that the expression of CD1d in monocytes was upregulated by RA. However, it is unknown whether αGalCer, a ligand for CD1d, is also able to regulate CD1d or whether it is able to synergize with RA to further upregulate CD1d. We show here using the THP-1 human monocytic cell line that αGalCer is unable to regulate the expression of CD1d. Moreover, we have clarified the kinetics of CD1d protein upregulation by showing that RA maximally upregulates the CD1d protein (p<0.001) within 24 hours. Also, it was reported that αGalCer was able to activate splenic B cells through CD1d in mice. However, it is unknown whether αGalCer is able to activate human B cells or whether it is able to synergize with RA to further induce activation. We show here using the CL-01 human B cell line that αGalCer is able to activate human B cells by upregulating the proliferation marker Ki67. We also show that the mechanism of human B cell activation occurs through the upregulation of the B cell transcription factor Pax5 (p<0.05) and the B cell coreceptor CD19 (p<0.05). These findings suggest that RA and αGalCer are potent regulators of APCs and could be useful as adjuvants to boost immunity after vaccination.