Secondary lymphoid organs (SLOs), including lymph nodes, tonsils and Peyer’s patches, contain highly organised microenvironments in which adaptive and innate immune cells interact with stromal fibroblasts. It is within these organs that germinal centres (GCs) form; structures that function to permit the development of high affinity antigen-specific humoral immune responses. Follicular dendritic cells (FDCs) and B cells are the cells primarily responsible for driving formation and function of the GC. B cells scan FDC stromal cell networks for antigen complement complexes bound to the CD21 receptor through the complement component C3dg. CD21 is expressed on both cell types, permitting transfer of antigen complexes from B cells to FDCs where it is retained and presented permitting antigen-specific B cell activation and initiating a cyclical cycle of selection and expansion leading to high affinity antibody selection. Human FDCs are reported to express a long isoform of the CD21 receptor (CD21L), whereas B cells express a short isoform (CD21S). In this thesis I utilised a flow cytometry-based assay to investigate the different potential mechanism of CD21 isoform function in B cells and FDCs; revealing that FDC express a significantly higher number of CD21 molecules on their cell surface and provide evidence that this may be a mechanism of antigen transfer between the two cells types. CD21 and the complement pathway, including C3 and its derivatives, have been implicated in autoimmune diseases, including Rheumatoid Arthritis (RA). Soluble CD21 (sCD21) concentration is consistently decreased within the serum of RA patients compared with age-matched healthy control samples. Here I show that lower sCD21 concentrations correlate with increased disease phenotype. Additionally, I show that sCD21 can block C3dg complex binding to peripheral B cells and consequently prevent co-activation through the CD19/CD21 complex on the surface of B cells. Together these results suggest a role for sCD21 in suppressing human immune responses.