FDC-SP Related Peptides Products

Definition

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.             

Related Peptides

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.

Discovery

Marshall et al reported the discovery of the FDC gene encoding the FDC-secreted protein in 2002¹.

Structural Characteristics

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 proteases^1,3.

Mode of Action

FDC-SP functions in intercellular communication by binding target cells through a specific signaling receptor, analogous to cytokines/chemokines. While FDC-SP does not share significant primary sequence homology with cytokines or chemokines, the overall amino acid composition, molecular mass, and charge (pI) of FDC-SP is similar to known inflammatory mediators such as IL-8. Furthermore, FDC-SP is linked to the cluster of alpha-chemokines on chromosome 4q13 that includes IL-8 and other proinflammatory chemokines¹.

Functions

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 cells^1,3. 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.

References

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.