ON THE KEY ROLE OF SECONDARY LYMPHOID ORGANS IN ANTIVIRAL IMMUNE-RESPONSES STUDIED IN ALYMPHOPLASTIC (ALY ALY) AND SPLEENLESS (HOX11(-/-)) MUTANT MICE/

The role of the spleen and of other organized secondary lymphoid organ s for the induction of protective antiviral immune responses was evalu ated in orphan homeobox gene II knockout mice (Hox11(-/-)) lacking the spleen, and in homozygous alymphoplastic mutant mice (aly/aly) posses sing a structurally altered spleen but lacking lymph nodes and Peyer's patches. Absence of the spleen had no major effects on the immune res ponse, other than delaying the antibody response by 1-2 d. In aly/aly mice, the thymus-independent IgM response against vesicular stomatitis virus (VSV) was delayed and reduced, whereas the T-dependent switch t o the protective IgG was absent. Therefore, aly/aly mice were highly s usceptible to VSV infection. Since aly/aly spleen cells yielded neutra lizing IgM and IgG after adoptive transfer into recipients with normal ly structured secondary lymphoid organs, these data suggest that the s tructural defect was mainly responsible for inefficient T-B cooperatio n. Although aly/aly mice generated detectable, but reduced, CTL respon ses after infection with vaccinia virus (VV) and lymphocytic choriomen ingitis virus (LCMV), the elimination of these viruses was either dela yed (VV) or virtually impossible (LCMV); irrespective of the dose or t he route of infection, aly/aly mice developed life-long LCMV persisten ce. These results document the critical role of organized secondary ly mphoid organs in the induction of naive T and B cells. These structure s also provide the basis for cooperative interactions between antigen- presenting cells, T cells, and B cells, which are a prerequisite for r ecovery from primary virus infections via skin or via blood.