Oral Presentations - Pathology and Laboratory Medicine - University ...

Post-doctoral FellowAbstract # 73Lenka L. Allan, Annelein M. Stax, Dong-Jun Zheng, Brian K. Chung, Rusung Tan,and Peter van den ElzenDepartment of Pathology, Child and Family Research Institute, University of British Columbia,Vancouver, BC, CanadaLenka Allanregulation of cd1d expression in human b cells byretinoic acid receptorBackround/ObjectivesProfessional antigen presenting cells, including B cells, utilize CD1d to present lipids to NKT cells. NKT cells areinnate-like lymphocytes that express a characteristic semi-invariant T cell receptor, which recognizes lipids includingthe potent glycolipid antigen -galactosylceramide (GalCer). B cells have been shown to present lipid antigens and torecruit cognate NKT cell help for lipid-directed antibody production. Given the newfound contribution of NKT cellsto humoral immune responses, we sought to identify the pathways that regulate CD1d expression in B cells.MethodsB cell CD1d expression was measured by FACS and qRT-PCR. The ability of B cells to present GalCer to co-culturedNKT cells was assessed by monitoring proliferation and cytokine secretion.ResultsHere we report that activated human B cells express lower levels of CD1d, compared to resting human B cells.Previous studies report that, in dendritic cells, PPAR ligands regulate CD1d expression via the induction of retinoicacid synthesis, which in turn directly up-regulates CD1d expression. We found that RAR ligands (ATRA andAM580), but not PPAR ligands, profoundly up-regulate human B cell expression of CD1d in vitro. RAR ligandtreatmentof B cells enhances their ability to present GalCer as well as stimulate NKT cell proliferation and activation.Moreover, NKT cells augmented proliferation of co-cultured AM580-treated B cells at lower GalCer concentrations.Higher GalCer concentrations instead promoted NKT cell cytotoxicity significantly reducing B cell numbers.ConclusionWe propose that RAR is an important physiological regulator of CD1d expression in B cells. These data furtherprovide a candidate mechanism that underpins NKT cell help for naïve B cells. Our data further demonstrate thatdownregulation of CD1d immediately following B cell activation may be necessary in order to evade NKT cellregulation/killing.84 2 0 1 0 * P o s t e r P r e s e n t a t i o n s