Follicular dendritic cell-secreted protein (FDC-SP) is expressed by activated follicular dendritic cells from human tonsils and FDC-like cell lines activated by TNF-alpha and specifically binds to activated B cells1.
FDC-SP is expressed specifically in periodontal ligament and parotid gland, and has molecular properties similar to those of statherin, a protein in saliva thought to function in preventing calcium precipitation. Both molecules are small in size (68 and 43 residues for mature human FDC-SP and statherin, respectively) and have a proline-rich region in their C-terminal half. In addition, these regions show high degree of hydrophobicity in contrast to their N-terminal hydrophilic regions. Such structural similarities strongly suggested that additional roles for FDC-SP exist and that additional experiments looking for functional similarities between FDC-SP and statherin would be very informative2.
Marshall et al reported the discovery of the FDC gene encoding the FDC-secreted protein in 20021.
Human and mouse FDC- secreted proteins are structurally unique, containing a conserved N-terminal charged region adjacent to the leader peptide. FDC-SP undergoes heterogeneous post-translational modification during biosynthesis and trafficking through the secretory pathway. The pairs of basic residues flanking the proline-rich sequence of FDC-SP might be important for its function, as such dibasic motifs are known to be potential target sites for cleavage by proteases1,3.
Mode of Action
FDC-SP can induce chemotaxis of CD40 stimulated non-transgenic B-cells and can significantly enhance B-cell migration in combination with chemokines, indicating that FDC-SP may function in part by regulating B-cell chemotaxis. FDC-SP may function by binding to and influencing the behavior of immune cells. FDC-SP regulates GC (germinal centre) initiation and maintenance by acting upon newly activated B cells transiting from the T zones. To our knowledge, FDC-SP is the first FDC-restricted gene product that binds to activated but not resting B cells1,3. FDC-SP may play an important role, adsorbing onto the surface of cementum and alveolar bone adjacent to periodontal ligament and onto tooth surface at the gingival crevice2.
1. Aaron J. Marshall, Quijiang Du, Kevin E. Draves, Yasufumi Shikishima, Kent T (2002). HayGlass, and Edward A. Clark. 2002. FDC-SP, a Novel Secreted Protein Expressed by Follicular Dendritic Cells. J Immunol., 169, 2381-2389.
2. Shinomura T, Nakamura S, Ito K, Shirasawa S, Höök M and Kimura JH (2008). Adsorption of follicular dendritic cell-secreted protein (FDC-SP) onto mineral deposits. Application of a new stable gene expression system. J Biol. Chem., 283 (48), 33658-64.
3. Al-Alwan M, Du Q, Hou S, Nashed B, Fan Y, Yang X and Marshall AJ (2007). Follicular Dendritic Cell Secreted Protein (FDC-SP) Regulates Germinal Center and Antibody Responses. J Immunol., 178, 7859 -7867.
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