A phenotypically dominant regulatory mechanism suppresses major histocompatibility complex class II gene expression...

The expression of major histocompatibility complex (MHC) class II antigens is down-regulated when B cells differentiate into plasma cells. We have studied the mechanism of down-regulation of MHC class II expression in a BALB/c strain-derived murine plasmacytoma cell line, NS1. NS1 cells express MHC class I antigens but not MHC class II antigens. We tested 20 uncloned hybrid cell lines obtained from the fusion of NS1 cells with MHC class II-expressing splenic B cells prepared from CBA, SJL or BALB/c mice. All the hybrid cell lines expressed MHC class I antigens of either or both parental haplotypes but did not express MHC class II. One NS1 X splenic B cell hybrid clone, K3, was used to further validate these results; K3 cells expressed MHC class I but not MHC class II antigens. K3 was fused to the MHC class II-expressing B lymphoma A20, and the seven resulting hybrid cell lines were again found to express MHC class I but not MHC class II antigens. Since NS1 is a subclone of the P3-X63Ag8 murine plasmacytoma, we also tested one P3-X63Ag8 x splenic B cell hybrid, Sp2/0, and two Sp2/0 x splenic B cell hybrids. All were found to express the appropriate MHC class I antigens but did not express MHC class II. Thus, our results suggest that the NS1 plasmacytoma suppresses MHC class II expression by a phenotypically dominant regulatory mechanism. We found that NS1 cells express correctly sized mRNA for the MHC class II genes A alpha, E alpha and the invariant chain. The co-expression of MHC class I protein and I-A and I-E region gene transcripts provides strong evidence that the MHC gene cluster is structurally intact, and that lack of class II expression is due to a genetic regulatory mechanism. The amounts of class II mRNA expressed by NS1 cells were at least equivalent to those found in splenic lymphocytes. Therefore, this regulation must operate post-transcriptionally.