RELT stains prominently in B cell lymphomas and binds proteins associated with leukemia

Abstract

Receptor Expressed in Lymphoid Tissues (RELT) is a human TNFR that is expressed prominently in the hematopoietic system and negatively regulates T-cell activation in mice. RELT has two identified homologous binding partners, RELL1 and RELL2. This study sought to further elucidate the function of RELT by identifying novel protein interactions with RELT family members and to study the localization of RELT in both normal and diseased tissues. A yeast two-hybrid screen identifed Phospholipid Scramblase 1 (PLSCR1) and MyoD family inhibitor domain-containing protein (MDFIC) as potential RELT-family member binding proteins that were confirmed by in vitro co-immunoprecipitations. PLSCR1 has been demonstrated to possess anti-leukemic properties, and RELT expression results in an altered cellular localization of PLSCR1 as determined by immunofluorescence (IF). The MDFIC gene encodes for a transcription factor and is located proximally to regions of chromosome 7 (7q31.1) frequently lost in AML patients. MDFIC was observed to co-localize with RELL1 at the plasma membrane and co-localize with RELT in intracellular compartments as determined by IF. Since RELT, PLSCR1 and MDFIC are prominently expressed in the hematopoietic system, we sought to characterize the expression of RELT in both normal lymph nodes and B cell lymphomas. Immunohistochemistry revealed a higher intensity of RELT staining in germinal centers in comparison to surrounding lymph node regions. Interestingly, the level of RELT staining increased progressively in low and high-grade B cell lymphomas versus normal lymph nodes. Collectively, these results further our understanding of proteins that interact with RELT and identify an association of RELT with B cell lymphomas.