FDC-SP, a Novel Secreted Protein Expressed by Follicular Dendritic Cells

Abstract

To define better the molecular basis for follicular dendritic cell (FDC) function, we used PCR-based cDNA subtraction to identify genes specifically expressed in primary FDC isolated from human tonsils. In this work we report the discovery of a novel gene encoding a small secreted protein, which we term FDC-SP (FDC secreted protein). The FDC-SP gene lies on chromosome 4q13 adjacent to clusters of proline-rich salivary peptides and C-X-C chemokines. Human and mouse FDC-SP proteins are structurally unique and contain a conserved N-terminal charged region adjacent to the leader peptide. FDC-SP has a very restricted tissue distribution and is expressed by activated FDCs from tonsils and TNF-α-activated FDC-like cell lines, but not by B cell lines, primary germinal center B cells, or anti-CD40 plus IL-4-activated B cells. Strikingly, FDC-SP is highly expressed in germinal center light zone, a pattern consistent with expression by FDC. In addition, FDC-SP is expressed in leukocyte-infiltrated tonsil crypts and by LPS- or Staphylococcus aureus Cowan strain 1-activated leukocytes, suggesting that FDC-SP can also be produced in response to innate immunity signals. We provide evidence that FDC-SP is posttranslationally modified and secreted and can bind to the surface of B lymphoma cells, but not T lymphoma cells, consistent with a function as a secreted mediator acting upon B cells. Furthermore, we find that binding of FDC-SP to primary human B cells is markedly enhanced upon activation with the T-dependent activation signals such as anti-CD40 plus IL-4. Together our data identify FDC-SP as a unique secreted peptide with a distinctive expression pattern within the immune system and the ability to specifically bind to activated B cells.

Adsorption of Follicular Dendritic Cell-secreted Protein (FDC-SP) onto Mineral Deposits

“…Expression of FDC-SP was observed at a high level in the junctional epithelium in addition to other structures such as tonsils, prostate gland, lymph nodes, and trachea, which all play a role in host defense (1,3). In addition, the proline-rich region in the C-terminal domain of FDC-SP has some structural similarity to an antimicrobial peptide Bac5 (20).…”

“…Although Marshall et al (1) reported that FDC-SP showed significant binding to B cells, its physiological function in oral tissues is not known. In this study, we investigated the binding capacity of FDC-SP to mineral based on its structural similarity to statherin, which is tightly adsorbed to hydroxyapatite (5).…”

“…2 is a small secretory protein that was originally identified in primary follicular dendritic cells isolated from human tonsils (1) and was implicated in modulation of B cell activity (2). Recently, we have found that 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 (3).…”

Sonic Hedgehog Is Produced by Follicular Dendritic Cells and Protects Germinal Center B Cells from Apoptosis

“…During the GC reaction, Ag-activated B cells move into the FDC network and replace the primary resting B cells that are initially located within the FDC reticulum of the primary follicles (32,53). Up-regulation of the expression of several surface cell markers, i.e., FDC-M1, Fc⑀RII/CD23, Fc␥RII/ CD32, VCAM1/CD106, MAdCAM-1 (54 -57), and some soluble factors such as IL-6 and FDC-SP (38,58), is a common feature of the development of the FDC network after immunization and reflects the involvement of those molecules in the maturational events associated with GCs. These membrane Ags and secreted proteins constitute indicators of FDC maturation and activation, and Shh could now be considered a new member of this group.…”

Human Follicular Dendritic Cells Express Prostacyclin Synthase: A Novel Mechanism to Control T Cell Numbers in the Germinal Center

“…For example, DRC-1, Ki-M4, 7D6, and HJ2 stain B cells (13,16,18), while 12B1 cross-reacts with monocytes (15), AS02 with blood stem cells (22), and CNA4.2 with T cells (17). In addition, FDC-SP, a recently discovered novel FDC molecule, is induced on cultured PBMC (23). Because mAb 3C8 that was developed in our laboratory did not display cross-reactivity with bone marrow-derived cells but specifically recognized FDCs in the GC (24,25), we reasoned that identification of the Ag would reveal novel molecular mechanisms to explain biological functions of FDC.…”