CRUCIAL ROLE OF TUMOR-NECROSIS-FACTOR RECEPTOR-1 EXPRESSION ON NONHEMATOPOIETIC CELLS FOR B-CELL LOCALIZATION WITHIN THE SPLENIC WHITE PULP

During immune responses the initial activation of B cells takes place in T cell zones of periarteriolar lymphoid sheaths (PALS) of the splen ic white pulp. After initial activation, B cells migrate into the prim ary follicles and, in association with follicular dendritic cells (FDC s), undergo clonal expansion and differentiation giving rise to germin al centers (GCs). Peanut agglutinin binding (PNA(+)) cells of the GC d ifferentiate further into memory or plasma cells. Here we report that in tumor necrosis factor receptor 1-deficient mice (TNFR1(-/-)), the l ocation of B cells was altered and that plasma cells were abnormally d istributed ill the splenic PALS. In contrast to lymphotoxin alpha-defi cient mice (LT alpha(-/-)), bone marrow or fetal liver transplantation did not correct the abnormal organization of the spleen, location of B cells, the lack of an FDC network, nor the antibody response in TNFR 1(-/-) mice, These results argue for a crucial role of TNFR1 expressio n on nonhematopoietic cells for the maintenance of the splenic archite cture and proper B cell location. In addition, the lack in development of an FDC network after adoptive transfer suggests that either FDCs a re not of bone marrow origin or that they depend on signals from nonhe matopoietic cells for maturation.