Lymphotoxin beta receptor signaling plays a crucial role in development of secondary lymphoid Talsupram hydrochloride organs. Surface lymphotoxin is a transmembrane heterotrimeric protein that belongs to the tumor necrosis factor family and is expressed by lymphoid tissue inducer cells during early phases of SLO formation. Acting through LTbR on lymphoid tissue organizer cells and earlier on their mesenchimal precursors, it activates synthesis of chemokines, adhesion molecules and lymphangiogenic factors through classical and alternative NFkB pathways, leading to maturation of stroma and lymphocyte homing. In postnatal period, LTbR signaling is required for follicular dendritic cell maintenance and germinal center formation in lymph nodes. And it is even more important in spleen, where postnatal LTbR-Ig treatment leads to disruption of follicles and marginal zone, as well as GC Sphingosine-1-phosphate failure. Clusterin, and X-ray�Cinducible transcript 8) was first described as the major glycoprotein in ram rete testis fluid with the capacity to elicit clustering of cells in an in vitro assay. It is a multifunctional protein, which is mainly studied for its role in neurodegeneration and cancer. Its mRNA is present at relatively high levels in brain, ovary, testes, liver, heart and adrenal gland; at moderate levels in spleen, lung, breast, kidney, seminal vesicle, prostate, and uterus; at low levels in skin, bone, thymus and digestive tract; and is absent in T-lymphocytes. Clusterin participates in tissue remodeling, apoptosis, lipid transport, complement-mediated cell lysis, and serves as an extracellular chaperone. At the protein level, clusterin was found in non-lymphoid cells of many SLO: gut-associated lymphoid tissue, Waldeyer��s ring, reactive tonsils, lymph nodes and spleen, but virtually nothing is known about its function in these organs. Clusterin is also present in medullary epithelial stromal cells of the primary lymphoid organ – thymus, but its precise function there is also not clear. In the present work we used expression profiling to identify new potential target genes of LTbR signaling pathway by comparing transcriptomes of spleen stromal cells derived from wild type and LTbR knock-out mice. Since LTbR signaling drives morphogenesis and functional maturation of SLO, we expected to find new immunity-relevant genes among its targets. After filtration of the microarray results we focused on clusterin as it was significantly downregulated in LTbR-deficient spleen at both mRNA and protein level and its function in the immune system was poorly studied. We demonstrated activation of clusterin gene transcription upon interaction of mouse embryonic fibroblasts with lymphoid cells bearing LT and significant changes in clusterin protein level and tissue distribution during primary immune response to T-dependent antigen. There are several CLU protein isoforms encoded by two CLU gene transcripts. The main and longer gene transcript encodes glycosylated presecretory form psCLU with apparent molecular weight of about 60 kDa.