THE LYMPHOTOXIN BETA-RECEPTOR CONTROLS ORGANOGENESIS AND AFFINITY MATURATION IN PERIPHERAL LYMPHOID-TISSUES

Lymphotoxin beta receptor (LT beta R)(-/-) mice were created by gene t argeting. LTPR-/- mice lacked Peyer's patches, colon-associated lympho id tissues, and ail lymph nodes. Mucosa patrolling alpha(E)beta(7)(hig h) integrin(+) T cells were virtually absent. Spleens lost marginal zo nes; T/B eel segregation and follicular dendritic cell networks were a bsent. Peanut agglutinin(+) cells were aberrantly detectable around ce ntral arterioles. In contrast to TNF receptor p55(-/-) mice, antibody affinity maturation was impaired. Since LT beta R-/- mice exhibit dist inct defects when compared to LT alpha(-/-) and LT beta(-/-) mice, it is suggested that the LT beta R integrates signals from other TNF fami ly members. Thus, the LT beta R proves pivotal for the ontogeny of the secondary lymphoid tissues. Furthermore, affinity maturation is depen dent on LT alpha(1)beta(2) rather than on LT alpha(3).