A limited number of genes are involved in the differentiation of germinal center B cells.
Mature B cells, upon activation, progressively differentiate through centroblasts into centrocytes and finally to plasmacytes that express large amounts of selected immunoglobulins. A significant part of this maturation is thought to involve induction of the unfolded protein response (UPR). We have compared gene expression in normal germinal center centroblasts, centrocytes, lymphoblastoid cells undergoing induced UPR, and the CCL155 plasmacytoma cell line. In the centroblast to centrocyte transition there is a change in the expression of a relatively small number of genes. These include a limited subset of the genes upregulated by a fully activated UPR as well as a small number of other transcription factors, some disulphide isomerases, and other genes. This is consistent with a model in which this transition is mediated by changes in the levels of expression of transcription factor B-lymphocyte-induced maturation protein 1 (Blimp1) (PRDM1), BACH2, X-box binding protein 1 (XBP1), interferon regulatory factor 4 (IRF4), and possibly vitamin D receptor (VDR) expression, together with post-transcriptional changes and a limited induction of aspects of the UPR.
Nakayama
Yasuhiro
Y
Department of Genetics, Yale University School of Medicine, 300 Cedar St., New Haven, Connecticut 06510, USA. yasuhiro.nakayama@yale.edu
Stabach
Paul
P
Maher
Stephen E
SE
Mahajan
Milind C
MC
Masiar
Peter
P
Liao
Cheng
C
Zhang
Xueqing
X
Ye
Zhi-jia
ZJ
Tuck
David
D
Bothwell
Alfred L M
AL
Newburger
Peter E
PE
Weissman
Sherman M
SM
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004229:Dithiothreitol / Q000378:metabolism; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000166:cytology*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D017510:Protein Folding; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014415:Tunicamycin / Q000378:metabolism; D000071717:X-Box Binding Protein 1
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D014415:Tunicamycin; D004229:Dithiothreitol