Our group has continued generation and characterization of a panel of mice with conditionally targeted TNF, LTa and LTb genes. We have documented the role of TNF or LT produced by B cells in the maintenance of the microarchitecture of lymphoid organs. Requirements in different lymphoid organs are distinct, and the role of LT versus TNF is different in spleen versus lymph nodes or Peyer's patches. We are in the process of characterization of inducible TNF and LT knockouts which may become valuable murine models for human subjects on TNF/LT blockers (such as RA patients). The distinct features in this panel of conditional knock-out are being correlated with the expression pattern of specific genes, including lymphoid tissue chemokines, adhesion molecules and several novel genes. Additionally, we have generated mice with combined p53.TNF/LT. p53.TNF and p53-LTa deficiencies and observed that the deletion of TNF/LT locus, but not of TNF, results in significant extension of the life span of p53-/- mice.