Differentiation‐specific expression of a novel G protein‐coupled receptor from Burkitt's lymphoma

Abstract

Deregulation of the proto-oncogene MYC by specific chromosomal translocations has been shown to be essential but not sufficient for the development of Burkitt's lymphoma (BL). To identify other genes which either mark important steps in tumorigenesis or which reflect the cellular differentiation state of BL cells we have compared tumor cells to immortalized lymphoblastoid B cells by subtractive hybridization. We have identified a complementary DNA clone which encodes a novel member of the superfamily of GTP-binding (G) protein-coupled receptors, designated BLR1. The corresponding mRNA is expressed in BL and lymphatic tissues but not in other cell lines either of the B cell lineage or of other hematopoietic or non-hematopoietic origin. This exclusive expression of BLR1 and the oncogenic potential of this receptor class supports the hypothesis that BLR1 exerts a regulatory function in BL lymphomagenesis and/or B cell differentiation. Moreover, the protein sequence is highly related to that of receptors for the cytokine interleukin (IL)-8 and other neutrophil chemoattractants. We conclude that BLR1 may represent a potential candidate involved in the process of physiologic trafficking, cell-cell interactions, and activation of mature B lymphocytes in lymphatic tissues.

Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome

“…In this context, the CXCL13-CXCR5 pairing has been shown to be critically involved in the homing of B cells into lymphoid follicles, as well as in the development of organized lymphoid follicles (28,29,40,41). The formation of ectopic lymphoid tissue in chronic inflammatory disease, such as primary SS, is a complex process regulated by an array of cytokines, adhesion molecules, and chemokines (4,13), partly mimicking signals found in normal lymphoid organogenesis (42).…”

“…Each of the subsets manifested a comparable high frequency of positive cells (mean Ϯ SD 46.4 Ϯ 2.5% in healthy subjects versus 46.1 Ϯ 7.7% in patients with primary SS). Notably, a significantly enhanced frequency of CD27Ϫ naive B cells that expressed CXCR4 transcripts was Both known CXCR5-mRNA splice variants (variant 1 NM_001716 and variant 2 NM_032966; National Center for Biotechnology Information database [28,29]) were analyzed in healthy controls and in patients with primary SS. It was found that individual peripheral B cells expressed either variant 1 (which encodes a protein that is 45 amino acids longer at the N-terminus than isoform 2) or variant 2.…”

The murine chemokine receptor CXCR4 is tightly regulated during T cell development and activation

“…The observed 91% homology between mouse and human CXCR4 is exceptionally high for members of the chemokine receptor family as only 83% for homology has been reported for human and mouse BLR1/CXCR5 [29,30], 78% homology for CCR1 [31,32], and 63% for CCR3 [32,33]. Together with the fact that SDF-1 shows 99% identity between both species, one is tempted to speculate that both receptor and ligand might serve identical functions in both species.…”

Expression Profiling of Murine Double-Negative Regulatory T Cells Suggest Mechanisms for Prolonged Cardiac Allograft Survival

“…In the present study, we report that CXCR5 gene expression is increased ϳ50-fold in both of the DN Treg clones compared with their mutant progeny. CXCR5 was described initially in Burkitt's lymphoma as a G protein-coupled receptor (45) and subsequently found in B cells and a subset of CD4 ϩ T cells (46). More recently, CXCR5 expression has also been shown in DN T cells from MRL-Lpr mice (47).…”