IgM and stromal cell-associated heparan sulfate/heparin as complement-independent ligands for CD19.

The more severe phenotype of mice lacking CD19 as compared to CD21 suggests that a complement-independent ligand for the CD19/CD21 complex exists. We sought ligands for CD19 by examining binding reactions with fusion proteins comprised of the extracellular region of CD19 and the Fc region of IgG1. A fusion protein containing the third extracellular domain (D3-Fc) bound to WEHI-231 cells, and this was competed by soluble IgM. This function of IgM was confirmed by the binding of D3-Fc to beads coated with IgM. A second ligand for D3-Fc was found on stromal cells, and was shown to be heparin/heparan sulfate. These two ligands would be considered to reside on follicular dendritic cells, and may account for the observed ability of D3-Fc to bind to sites in germinal centers containing these cells.