The NF-κB family member, c-Rel plays a critical role in the regulation of immune function. It was found that mice with c-Rel deficiency exhibited extensive defects in the survival of lymphocytes and cell cycle progression, and were tolerant to allografts. To further characterize the regulatory function of c-Rel, a representational difference analysis (RDA) was performed on mRNAs derived from B lymphocytes of wild type and the c-Rel knockout mice. By using this approach, a novel gene designated as lymphocyte-derived C-type lectin-1 (LCL-1) was identified, whose expression was dependent on the intact c-Rel molecule. In the present study, LCL-1 was demonstrated to be a type Ⅱ transmembrane protein with a single extracellular carbohydrate recognition domain (CRD) that exhibited significant degree of homology to C-type lectin-like receptors, including CD69. This LCL-1 gene was found to be located at the NK gene complex (NKC) on mouse chromosome 6 and could encode at least 4 alternatively spliced isoforms. In addition to its expression on B lymphocytes, it was also expressed on immature as well as mature dendritic cells (DCs), especially with higher expression level on mature DCs. Together, our findings explore one new member of the NKC family and demonstrate for the first time that a lectin-like receptor of the the NKC family is the target gene of c-Rel. The was found that mice with c-Rel fragmentary defects in the survival of lymphocytes and cell cycle progression, and were tolerant to allografts. The NF-κB family member, c-Rel plays a critical role in the regulation of immune function. To further characterize the regulatory function of c-Rel, a representational difference analysis (RDA) was performed on mRNAs derived from B lymphocytes of wild type and the c-Rel knockout mice. By using this approach, a novel gene designated as lymphocyte-derived C-type lectin-1 (LCL-1) was identified, whose expression was dependent on the intact c-Rel molecule. In the present study, LCL-1 was demonstrated to be a type II transmembrane protein with a single extracellular carbohydrate recognition domain (CRD) that showed significant degree of homology to C-type lectin-like receptors, including CD69. This LCL-1 gene was found to be located at the NK gene complex (NKC) on mouse chromosome 6 and could encode at least 4 alternatively In addition to its expression on B lymphocytes, it was also expressed on immature as well as mature dendritic cells (DCs), especially with higher expression level on mature DCs. Together, our findings explore one new member of the NKC family and demonstrate for the first time that a lectin-like receptor of the NKC family is the target gene of c-Rel.