Follicular Dendritic Cell Secreted Protein (FDC-SP) Regulates Germinal Center and Antibody Responses

Abstract

We previously identified follicular dendritic cell secreted protein (FDC-SP), a small secreted protein of unknown function expressed in human tonsillar germinal centers (GC). To assess potential in vivo activities of FDC-SP, transgenic mice were generated to constitutively express FDC-SP in lymphoid tissues. FDC-SP transgenic mice show relatively normal development of immune cell populations, with the exception of a small increase in mature follicular B cells, and normal lymphoid tissue architecture. Upon immunization with a T-dependent Ag, FDC-SP transgenic mice were capable of producing an Ag-specific Ab; however, the titers of Ag-specific IgG2a and IgE were significantly reduced. GC responses after immunization were markedly diminished, with transgenic mice showing decreased numbers and sizes of GCs but normal development of follicular dendritic cell networks and normal positioning of GCs. FDC-SP transgenic mice also showed reduced production of Ag-specific IgG3 Ab after immunization with a type II T-independent Ag, suggesting that the FDC-SP can also regulate the induction of B cell responses outside the GC. Purified FDC-SP transgenic B cells function normally in vitro, with the exception of blunted chemotaxis responses to CXCL12 and CXCL13. FDC-SP can induce the chemotaxis of CD40-stimulated nontransgenic 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. These results provide the first evidence for immunomodulatory activities of FDC-SP and implicate this molecule as a regulator of B cell responses.

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

“…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).…”

Maturation and beyond: proteins in the developmental continuum from enamel epithelium to junctional epithelium

“…In a ligature-induced model of periodontitis in rats the expression of FDCSP was significantly decreased during the establishment of periodontal attachment loss, while interleukin 17 (IL-17) and the RANKL/OPG ratio were up regulated, indicating a state of acute inflammation and increased bone resorption, respectively. This suggests a possible role for FDCSP in mediating the inflammatory responses to periodontal pathogens in the JE, and ties back to the documented immunmodulatory role of FDCSP (Al-Alwan et al, 2007; Hou et al, 2014). …”

Decreased expression of follicular dendritic cell–secreted protein correlates with increased immunoglobulin A production in the tonsils of individuals with immunoglobulin A nephropathy

“…Recently, studies have also suggested that acute stimulation by FDC-SP could potentially act in concert with CXC chemokines to enhance B-cell migration, whereas chronic exposure to high levels of FDC-SP can blunt their migratory responses. 11 In the absence of chronic exposure to high levels of FDC-SP, B cells in GCs in the tonsils of IgAN patients may present enhanced migratory responses from the dark zone to the light zone, where they undergo isotype switching, and differentiation into IgA 1 plasma cells or memory cells. Consistent with this, in a previous study, we had observed enhanced IgA class switching in the tonsils of IgAN patients, which correlated with the production of IgA in tonsils (data not shown).…”

“…9,10 Previous studies have reported that FDC-SP regulates GC and antibody responses. 11 More interestingly, a recent study has shown that FDC-SP controls IgA production 12 ; it is therefore possible that FDC-SP may be involved in IgA production in tonsils in individuals with IgAN. However, the mechanism by which FDC-SP may regulate production of IgA remains unclear.…”