THE SEQUENTIAL ROLE OF LYMPHOTOXIN AND B-CELLS IN THE DEVELOPMENT OF SPLENIC FOLLICLES

The transfer of lymphocytes into severe combined immunodeficiency (SCI D) mice induces a series of histological changes in the spleen, includ ing the appearance of mature follicular dendritic cells (FDCs). Studie s were undertaken to clarify the role of lymphotoxin (LT) in this proc ess. The results show that SCID mice have a small and partially differ entiated white pulp containing marginal zone and interdigitating dendr itic cells, but lacking FDCs. Transferred spleen cells can segregate i nto T and B cell areas shortly after their injection to SCID mice. Thi s ability is dependent on signaling through LT-beta receptor (LT-beta R), since blocking ligand-receptor interaction in recipient SCID mice ablates the capacity of the transferred cells to segregate. A week aft er lymphocyte transfer, host-derived FDCs appeared in the reconstitute d SCID mice. This induction of FDCs is dependent on LT-beta R signalin g by B cells since LT-alpha(-/-) B cells are incapable of inducing dev elopment of FDCs in SCID mice, even after cotransfer of LT-alpha(+/+) T cells. Therefore, LT plays at least two discrete roles in splenic or ganization. First, it appears that LT induces the differentiation of t he white pulp to create sites for lymphocyte segregation. Second, LT e xpression by B cells drives the maturation of FDCs and the organizatio n of B cell follicles.