ABSENCE OF LYMPH-NODES IN LYMPHOTOXIN-ALPHA(LT-ALPHA)-DEFICIENT MICE IS DUE TO ABNORMAL ORGAN DEVELOPMENT, NOT DEFECTIVE LYMPHOCYTE MIGRATION

Mice homozygous for a targeted null mutation of lymphotoxin-alpha (LT alpha) are born without lymph nodes (LN) or Peyer's patches (PP) and w ith altered splenic architecture. To investigate the mechanism of fail ed LN organogenesis, rue transferred bone marrow (BM) from Thy 1.2 LT alpha-deficient or Thy 1.2 wild type mice to lethally irradiated 8-12- week-old Thy 1.1 wild type recipients. Six to 10 weeks later, reconsti tution of LN and spleen with Thy 1.2 cells was similar whether the BM was derived from LT alpha-deficient or wild type donors. lit contrast, reconstitution of irradiated LT alpha-deficient mice with wild type B M did not induce the development of detectable LN, although reconstitu tion of the spleen occurred appropriately. The expression and regulati on of the lymphocyte adhesion molecule L-selectin from the LT alpha-de ficient mice appeared normal. These data indicate that LT alpha-depend ent interactions must occur during development in order for LN genesis to take place; however, lymphocyte expression of LT alpha is not requ ired for these cells to home to existing LN structures. (C) 1995 Wiley -Liss, Inc.