title: Partial plasma cell differentiation as a mechanism of lost major histocompatibility complex class II expression in diffuse large B-cell lymphoma.
abstract: Loss of major histocompatibility complex class II (MHC II) expression is associated with poor patient outcome in diffuse large B-cell lymphoma (DLBCL). As MHC II molecules are lost with plasmacytic differentiation in normal cells, we asked whether MHC II loss in DLBCL is associated with an altered differentiation state. We used gene expression profiling, quantum dots, and immunohistochemistry to study the relationship between MHC II and plasma cell markers in DLBCL and plasmablastic lymphoma (PBL). Results demonstrate that MHC II(-) DLBCL immunophenotypically overlap with PBL and demonstrate an inverse correlation between MHC II and plasma cell markers MUM1, PRDM1/Blimp1, and XBP1s. In addition, MHC II expression is significantly higher in germinal center-DLBCL than activated B cell-DLBCL. A minor subset of cases with an unusual pattern of mislocalized punctate MHC II staining and intermediate levels of mRNA is also described. Finally, we show that PBL is negative for MHC II. The results imply a spectrum of MHC II expression that is more frequently diminished in tumors derived from B cells at the later stages of differentiation (with complete loss in PBL). Our observations provide a possible unifying concept that may contribute to the poor outcome reported in all MHC II(-) B-cell tumors.
authors.affiliation: Department of Pathology, University of Arizona, 1501 N Campbell Avenue, Tucson, AZ 85724-5043, USA.
authors.forename: Sarah T
authors.initials: ST
authors.lastname: Wilkinson
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Vanpatten
authors.forename: Diane R
authors.initials: DR
authors.lastname: Fernandez
authors.forename: Patrick
authors.initials: P
authors.lastname: Brunhoeber
authors.forename: Karl E
authors.initials: KE
authors.lastname: Garsha
authors.forename: Betty J
authors.initials: BJ
authors.lastname: Glinsmann-Gibson
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Grogan
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
mesh_terms: D000704:Analysis of Variance; D018951:Antigens, CD20 / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071717:X-Box Binding Protein 1; D000099218:Interferon Regulatory Factor-4
chemical_list: D018951:Antigens, CD20; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D050835:Interferon Regulatory Factors; D000074462:Positive Regulatory Domain I-Binding Factor 1; D000071701:Regulatory Factor X Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; D000099218:Interferon Regulatory Factor-4; C000605543:XBP1 protein, human; C087042:PRDM1 protein, human