Host origin of follicular dendritic cells induced in the spleen of SCID mice after transfer of allogeneic lymphocytes

Abstract

Follicular dendritic cells (FDC) are uniquely characterized by the ability to trap immune complexes. In a previous report, it was shown that functional FDC with the capacity to trap immune complexes via complement receptor emerged in the splenic follicle after transferring syngeneic lymphocytes into the severe combined immunodeficiency (SCID) mouse. In the present report, we have investigated whether FDC are derived from haematopoietic cells or surrounding stromal components, by transferring allogeneic lymphocytes into SCID mice. Transfer of allogeneic T and B lymphocytes (H-2k) into SCID(H-2d) mice, however, failed to induce the development of FDC in the splenic white pulp. This was due to a graft-versus-host reaction (GVHR) by allogeneic lymphocytes against host stromal cells, as revealed by the destruction of the splenic reticular meshwork. The GVHR was prevented in transfer experiments of T-cell-depleted allogeneic lymphocytes with daily administration of anti-Thy-1 antibody. This resulted in segregated lodgement of allogeneic B lymphocytes in the proper compartments and, thereafter, generation of FDC in the primary follicle of SCID spleen, as revealed by the trapped immune complexes via complement receptors. The H-2 of the newly generated FDC was examined by two-colour immunofluorescent staining. FDC were defined as the reticular cells stained with anti-CR1/2 or FDC-M1 antibodies. FDC carried host H-2, clearly indicating that newly generated FDC are host-derived. In addition, the FDC shared the BP-3 protein with the surrounding reticular cells, a specific marker of reticular meshwork in the murine lymphoid tissues, and formed a network continuous with the rest of the reticulum, suggesting that FDC and non-FDC reticular cells belong to the same cell lineage.