The G protein‐coupled receptor BLR1 is involved in murine B cell differentiation and is also expressed in neuronal tissues

Abstract

The BLR1 gene, isolated initially from Burkitt's lymphoma cells (Eur. J. Immunol. 1992. 22: 2795), encodes a G protein-coupled receptor with significant relationship to receptors for chemokines (IL-8, MIP-1 alpha) and neuropeptides. The murine homologue of human BLR1 was cloned and used to investigate its expression in vivo. blr1-specific transcripts are observed in secondary lymphatic organs and to a lesser extent in brain of adult mice but not in other tissues. RNA in situ hybridization localizes blr1 transcription to primary follicles and to the mantle zone of secondary follicles. SCID mice in which mature B cell development is severely impaired exhibit a strongly reduced level of blr1-specific RNA in the spleen. The analysis of murine lymphoid tumor cell lines representing distinct stages of the B cell lineage reveals elevated expression of blr1 in B cell lymphomas but not in pre-B lymphomas or plasmacytomas. Induction of differentiation of resting B cells by cytokines or mitogens down-regulates expression of blr1. RNA in situ hybridization using brain sections of adult mice detects blr1 transcription in the granule and Purkinje cell layer of the cerebellum. Interestingly, the blr1 gene is also expressed during late embryogenesis in fetal liver and brain. In view of the remarkable expression pattern in the B cell lineage we suggest that murine BLR1 may represent a cytokine/neuropeptide receptor exerting regulatory functions on recirculating mature B lymphocytes.

Differential expression of chemokine receptors in B cell malignancies

“…Interestingly, we show that CXCR5 is down-regulated in HCL and completely absent in multiple myeloma. This latter observation confirms earlier findings of Fö rster et al using Northern blot hybridisation in murine plasmacytoma cell lines 20 and flow cytometry in one patient with multiple myeloma 13 and extends them to a larger patient cohort. Our data showing weak or even absent staining for CXCR5 on HCL and ALL cells, respectively (Table 1), contrast with those reported by Jones et al, 17 who demonstrated strong CXCR5 immunoreactivity on 30 cases of B cell lymphoma/leukemia corresponding to all maturational stages of B cell development.…”

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.…”

Chemokines and chemokine receptors in CNS pathology

“…One of them is CXCR5 receptor isolated initially from Burkitt's lymphoma cells but expressed also in mature B cells and in brain neurons (Kaiser et al, 1993).…”