LYMPHOTOXIN-ALPHA-DEFICIENT MICE - EFFECTS ON SECONDARY LYMPHOID ORGAN DEVELOPMENT AND HUMORAL IMMUNE RESPONSIVENESS

Targeted mutagenesis in embryonic stem cells was used to generate mice deficient in lymphotoxin-alpha (LT-alpha). Mice lacking LT-alpha(-/-) (LT-alpha(-/-) mice) exhibit a phenotype dominated by defects in seco ndary lymphoid organ development. LT-alpha(-/-) mice lack lymph nodes and Peyer's patches, and possess spleens in which the usual architectu re is disrupted. However, in a few of the mutants, abnormal lymph node -like structures were observed, mainly within the mesenteric fat. Abno rmal clusters of lymphocytes were also found to accumulate in the peri portal and perivascular regions of the liver and lung of LT-alpha(-/-) mice. Yet, lymphocytes from LT-alpha(-/-) mice appeared phenotypicall y normal, expressing the expected ratios of B and T cell surface marke rs as well as the lymphocyte homing marker, L-selectin. In addition, b one marrow cells from LT-alpha(-/-) mice were able to successfully rec onstitute the lymphoid organs of severe combined immunodeficient mice. However, LT-alpha(-/-) mutant mice examined for humoral immune respon siveness were found to be impaired in their ability to respond to diff erent Ag. These data illustrate the utility of this mouse model as a s ystem for understanding lymphoid organ development and its effects on immune responsiveness.