Heparan sulfate (HS) modulates many cellular processes including adhesion, motility, ligand-receptor interaction, and proliferation. Here I report that murine B cells express very little HS, and that upon either bacterial or viral infection, HS is rapidly upregulated at the surface of B cells. My thesis work first describes the molecular details of HS induction and regulation in B cells. I also describe the generation and characterization of mice that are unable to express heparan sulfate on B cells, which we used to investigate the role of HS expression on B cells in vivo. With this conditional knockout mouse, I show the importance of HS expression for the generation and/or maintenance of antibody producing cells during a viral infection. Finally, I show data that suggests that HS expression on B cells enhances the antibody response to antigens containing a heparan sulfate-binding domain. The work presented here provides the first detailed evaluation of HS expression on B cells. This work illustrates the importance of HS in the response to certain classes of antigens, as well as in the development of the B cell response.