Clusterin is a potential lymphotoxin beta receptor target that is upregulated and accumulates in germinal centers of mouse spleen during immune response.

Clusterin is a multifunctional protein that participates in tissue remodeling, apoptosis, lipid transport, complement-mediated cell lysis and serves as an extracellular chaperone. The role of clusterin in cancer and neurodegeneration has been extensively studied, however little is known about its functions in the immune system. Using expression profiling we found that clusterin mRNA is considerably down-regulated in mouse spleen stroma upon knock-out of lymphotoxin ß receptor which plays pivotal role in secondary lymphoid organ development, maintenance and function. Using immunohistochemistry and western blot we studied clusterin protein level and distribution in mouse spleen and mesenteric lymph nodes in steady state and upon immunization with sheep red blood cells. We showed that clusterin protein, represented mainly by the secreted heterodimeric form, is present in all stromal compartments of secondary lymphoid organs except for marginal reticular cells. Clusterin protein level rose after immunization and accumulated in light zones of germinal centers in spleen--the effect that was not observed in lymph nodes. Regulation of clusterin expression by the lymphotoxin beta signaling pathway and its protein dynamics during immune response suggest a specific role of this enigmatic protein in the immune system that needs further study.

In vitro selection of optimal RelB/p52 DNA-binding motifs.

Rel/NF-kB dimers of different subunit composition can activate distinct subsets of target genes in vivo, however, the role of DNA recognition in this specificity is not well understood. We set out to study the DNA-binding ability of RelB/p52, the least studied of all NF-kB proteins and the main transcriptionally active product of the alternative NF-kB signaling pathway. We searched for optimal binding sites for RelB/p52 by random site selection method, using full-length proteins expressed in eukaryotic cells. The subset of RelB/p52-binding sequences defines a consensus which is very similar to the classical RelA/p50 consensus. Importantly, each of these binding sites is also recognized by RelA/p50 heterodimer with comparable affinity, questioning the existence of RelB/p52-specific kappa B sites.