Coordinate loss of MHC class II expression in the diffuse large B cell lymphoma cell line OCI-Ly2 is due to a novel mutation in RFX-AP.

Loss of major histocompatibility complex class II (MHCII) antigen expression on diffuse large B cell lymphoma (DLBCL) corresponds closely with significant decreases in patient survival. However, the mechanisms accounting for MHCII loss in DLBCL have not been thoroughly characterized to date. In this report, we demonstrate that coordinate loss of MHCII expression in OCI-Ly2 DLBCL cells is associated with an 11-base deletion in the cDNA encoding RFX-AP, one of the subunits of the heterotrimeric regulatory factor X (RFX) that is required for activating MHCII transcription. This deletion results in a frameshift in the RFX-AP protein beginning at amino acid 234 and, therefore, in the loss of C-terminal amino acids that are required for function. Stable transfection of OCI-Ly2 DLBCL cells with an expression vector for wild-type RFX-AP restores MHCII expression, which strongly suggests that the defect in RFX-AP accounts for MHCII loss in these cells.

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