The lymphotoxin β receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues

Lymphotoxin beta receptor (LT beta R)(-/-) mice were created by gene targeting. LTPR-/- mice lacked Peyer's patches, colon-associated lymphoid tissues, and ail lymph nodes. Mucosa patrolling alpha(E)beta(7)(high) integrin(+) T cells were virtually absent. Spleens lost marginal zones; T/B eel segregation and follicular dendritic cell networks were absent. Peanut agglutinin(+) cells were aberrantly detectable around central arterioles. In contrast to TNF receptor p55(-/-) mice, antibody affinity maturation was impaired. Since LT beta R-/- mice exhibit distinct defects when compared to LT alpha(-/-) and LT beta(-/-) mice, it is suggested that the LT beta R integrates signals from other TNF family members. Thus, the LT beta R proves pivotal for the ontogeny of the secondary lymphoid tissues. Furthermore, affinity maturation is dependent on LT alpha(1)beta(2) rather than on LT alpha(3).