[Generation of artificial lymph nodes (aLNs) and their immunological function]

We demonstrated that artificial lymph nodes (aLNs) could be generated by the transplantation of stromal cell-embedded biocompatible scaffolds into the renal subcapsular space in mice. T and B cell domains that form in the aLNs have a similar function in the immune response as the follicles of normal lymphoid tissue. The aLNs were transplantable to naive normal as well as to severe combined immunodeficient (SCID) or RAG deficient mice where aLNs efficiently induced secondary immune responses. Antigen-specific secondary responses were strongly induced in aLNs even four weeks after their transplantation. The antigen-specific antibody responses in the lymphocyte-deficient SCID or RAG KO mice carrying aLNs were enormous, reaching 7-8mg/mL in serum. The cells from the aLNs migrated to the SCID or RAG KO mouse spleen and bone marrow where they expanded to generate large numbers of antigen-specific IgG-class antibody-forming cells. Secondary responses were maintained with time after antigen challenge, indicating that aLNs can support memory B cells and long lived plasma cells. To our surprise, memory type CD4+ T cells (CD44(hi), CD62L(lo)) were highly enriched in the aLNs as well as in spleens of SCID mice carrying the aLNs. These data indicate that the lymph node-like lymphoid tissues which were generated on stromal cell-embedded biocompatible scaffolds were easily transplantable and could mount a strong antigen specific humoral as well as cellular immune responses.