FCRL6 receptor: expression and associated proteins.

FCRL6 receptor is a more recently identified representative of the FCRL family. We generated a panel of mouse mAbs to baculovirus-derived recombinant FCRL6 protein. The clone 7B2 was found to specifically recognize a 63kDa protein expressed preferentially on the surface of CD8 T and CD56 NK cells in human peripheral blood and spleen. The clone 7B2 reacts with FCRL6 in Western blotting, FACS, and immunohistochemistry. In the T cell lineage, FCRL6 functions in antigen-experienced cells. Mitogenic stimulation of PB leukocytes in vitro resulted in an abrogation of the FCRL6 gene expression. We found a significant decrease in the FCRL6 gene expression in peripheral T cells of patients with certain autoimmune and blood diseases, and its upregulation at the late stages of HIV infection. Study of the FCRL6 association with signaling molecules showed its ability to recruit SHP-1, SHP-2, SHIP-1, and SHIP-2 phosphatases, and also adaptor protein Grb2 through phosphorylated cytoplasmic tyrosines. The current results demonstrate inhibitory potential of FCRL6 and suggest its possible involvement in modulation of CTL effector functions in various immune disorders.

CD150 regulates JNK1/2 activation in normal and Hodgkin's lymphoma B cells.

The CD150 receptor is expressed on thymocytes, activated and memory T cells, B cells, platelets, natural killer T cells, and mature dendritic cells, and is also detected on tumor cells of Hodgkin's lymphoma (HL) and diffuse large B-cell lymphoma with an activated B cell phenotype. Here, we report that the level of CD150 expression is elevated during B cell differentiation toward plasma cells. In primary tonsillar B cells and HL cell lines, CD150 signaling regulates the phosphorylation of three types of mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and Jun N-terminal kinase 1/2 (JNK1/2). CD150 induced ERK1/2 activation in primary tonsillar B cells and in two HL cell lines. CD150 mediated activation of JNK1/2 p54 and JNK2-gamma kinase isoforms in all CD150(+) B cell lines we tested. CD150 associated with the serine/threonine kinase hematopoetic progenitor kinase 1 (HPK1) regardless of CD150 tyrosine phosphorylation or binding of the SH2D1A adaptor protein to CD150, and HPK1 overexpression enhanced CD150-mediated JNK1/2 phosphorylation. CD150 ligation inhibited cell proliferation of all studied HL cell lines and induced apoptosis in L1236 HL cells that did not depend on JNK activity. As signaling through CD150 modulates MAPK activity in HL tumor cells, CD150 may contribute to regulation of tumor cell maintenance in low-rate proliferating HLs.