Heparan sulfate expression on B cells modulates IgM expression in aged mice and steady-state plasma cells

Abstract

Heparan sulfate (HS) modulates many cellular processes including adhesion, motility, ligand-receptor interaction, and proliferation. We have previously reported that murine B cells strongly upregulate cell surface HS upon exposure to type I interferon, TLR-ligands, or B cell receptor stimulation. To investigate the role of HS on B cells in vivo, we utilized EXT1lox/lox CD19-Cre conditional KO mice, which are incapable of synthesizing HS in B cells. We found that suppressing HS expression on B cells has no overt effect in B cell development, localization, or motility. However, we did observe that EXT1 conditional KO mice have decreased poly-reactive IgM in naive aged mice relative to littermate control mice. Despite this decrease in poly-reactive IgM, EXT1 conditional KO mice mounted a normal B cell response to both model antigens and influenza infection. We also observed decreased plasma cells in EXT1 conditional KO mice after influenza infection. Although EXT1 conditional KO mice have decreased plasma cells, these mice still had comparable numbers of influenza-specific antibody secreting cells to littermate control mice. The findings presented here suggest that HS expression on B cells does not play a major role in B cell development or overall B cell function but instead might be involved in fine-tuning B-cell responses.