Discriminating gene expression profiles of memory B cell subpopulations.
Morphologically and functionally distinct subpopulations of human memory B (B(Mem)) cells are identifiable by either their expression of CD27 or Fc receptor-like 4 (FCRL4), an immunoglobulin domain containing a receptor with strong inhibitory potential. We have conducted comparative transcriptome and proteome analyses of FCRL4(+) and FCRL4(-) B(Mem) cells and found that these two subsets have very distinctive expression profiles for genes encoding transcription factors, cell-surface proteins, intracellular signaling molecules, and modifiers of the cell-cycle status. Among the differentially expressed transcription factors, runt-related transcription factor 1 (RUNX1) transcript levels were up-regulated in FCRL4(-) cells, whereas RUNX2 transcripts were preferentially detected in FCRL4(+) cells. In vitro evidence for FCRL4 promoter responsiveness and in vivo promoter occupancy suggested that RUNX transcription factors are involved in the generation of these B(Mem) cell subpopulations. A distinctive signature profile was defined for the FCRL4(+) B(Mem) cells by their expression of CD11c, receptor activator for nuclear factor kappaB ligand, and FAS cell-surface proteins, in combination with increased levels of SOX5, RUNX2, DLL1, and AICDA expression. We conclude that this recently identified subpopulation of B(Mem) cells, which normally resides in epithelial tissue-based niches, may serve a unique role in mucosal defense and, conversely, as a target for neoplastic transformation events.
Ehrhardt
Götz R A
GR
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Hijikata
Atsushi
A
Kitamura
Hiroshi
H
Ohara
Osamu
O
Wang
Ji-Yang
JY
Cooper
Max D
MD
D015703:Antigens, CD / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002453:Cell Cycle; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007156:Immunologic Memory; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055755:SOXD Transcription Factors; D014157:Transcription Factors / Q000235:genetics
D015703:Antigens, CD; D050659:Core Binding Factor Alpha 1 Subunit; D050676:Core Binding Factor Alpha 2 Subunit; D004268:DNA-Binding Proteins; C423544:FCRL4 protein, human; D009687:Nuclear Proteins; D053245:RANK Ligand; D012333:RNA, Messenger; C493728:RUNX1 protein, human; C493709:RUNX2 protein, human; D011961:Receptors, Fc; C490301:SOX5 protein, human; D055755:SOXD Transcription Factors; C505688:TNFSF11 protein, human; D014157:Transcription Factors; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)