Induction of compartmentalized B-cell responses in human tonsils

Abstract

The capacity of tonsillar and nasal mucosal lymphoid tissues to serve as induction sites of local and/or distant B-cell responses in humans has been examined. The frequencies of vaccine-specific antibody-secreting cells (ASC) in cell suspensions from palatine tonsils (PT) and adenoids were determined after local (intra-tonsillar [i.t.]) and regional (intranasal [i.n.]) immunizations as well as peroral and parenteral immunizations with cholera and tetanus toxoids. While peroral and parenteral immunizations evoked negligible ASC responses in PT, i.t. vaccination induced a substantial ASC response which consisted of immunoglobulin G (IgG) and IgA ASC. Responses were highly restricted to immunized tonsils. Primary immunization in one PT followed by a second immunization of both PT evoked a larger ASC response in the primed tonsil. The latter ASC response was associated with higher frequencies of ASC precursors in primed tonsils. Furthermore, two i.n. immunizations induced only modest ASC responses in PT, although such immunizations evoked high ASC responses in adenoids. However, both i.t. and i.n. routes of immunization induced specific peripheral blood ASC responses, suggesting that a fraction of B cells activated in tonsils or in nasal mucosa may enter the circulation and disseminate to distant organs. These blood ASC responses preceded increases in both IgA and IgG antibody titers in nasal washes and serum samples. However, vaccine-specific ASC were not detected in duodenal cell suspensions from volunteers who had received i.t. or i.n. immunizations. Collectively, these results indicate that tonsils can serve as expression sites of locally induced antibody responses and support the development of immunological memory. Furthermore, tonsils may serve as powerful inductive sites for immune responses expressed in the upper aerodigestive tract.