Cellular Gatekeepers Of The Hurnoral Immune Response

The spleen is critical for eliminating bloodborne pathogens and preventing systemic infection. In the marginal zone (MZ), the site in which splenic antibody responses are first initiated, we have discovered a dendritic cell (DC) ‘hairnet’ architecture that is responsible for extracting two unrelated viral antigens from the perfusing blood and importing them into B cell follicle to initiate IgM and IgG responses. The IgM response was independent of T-cell help, and proceeded via DC display of conformationally intact antigen in the absence of MHC proteins. Interestingly the DC-antigen captures and importing mechanism are solely governed by the glycan of the antigens. Taking all together, we propose that DC hairnet architecture, inshealthing the MZ, constitutes a filtering device that capture and concentrates protein antigens in a glycan-dependent manner from solution and catalyzes their delivery to B cells follicle to initiate humoral immune responses.