FAILURE OF GERMINAL CENTER FORMATION AND IMPAIRMENT OF RESPONSE TO ENDOTOXIN IN TUMOR-NECROSIS-FACTOR ALPHA-DEFICIENT MICE

To study the pathophysiologic roles of TNF alpha, we produced TNF alph a gene-disrupted mice by gene targeting. TNF alpha-deficient mice deve lop normally without any alteration in the lymphocyte populations. How ever, in these mice, the germinal center formation in the peripheral l ymphoid organs failed in response to the T cell-dependent antigens. TN F alpha-deficient mice are resistant to lethal doses of endotoxin and D-galactosamine without hepatocyte apoptosis, yet demonstrate thymus a poptosis. Our results indicated an important role for TNF alpha in ger minal center formation and in the sepsis-induced hepatocyte apoptosis that precedes liver failure.