TRANSFER OF PRIMITIVE STEM PROGENITOR BONE-MARROW CELLS FROM LT-ALPHA(-/-) DONORS TO WILD-TYPE HOSTS - IMPLICATIONS FOR THE GENERATION OF ARCHITECTURAL EVENTS IN LYMPHOID B-CELL DOMAINS/

To analyze whether the phenotypic abnormalities observed in lymphotoxi n-alpha(-/-) (LT alpha(-/-)) mice are intrinsic to the hemolymphoid sy stem itself or dependent on stromal elements, wild-type (WT) mice were reconstituted with hone marrow (BM) cells enriched for hemopoietic se em cells from LT alpha(-/-) animals. WT mice reconstituted with LT alp ha(-/-)c-kit(+)Lin(-)Sca-1(+) BM cells do not maintain follicular dend ritic cell (FDC) networks and do not form primary follicles, while cle ar segregation of B and T cells could be observed. Furthermore, IgM(+) IgD(-) B cells, MOMA-1 (anti-metallophilic macrophages), ERTR-9 (anti- marginal zone macrophages), and MECA-367 (anti-MAdCAM-1) were all abse nt from the splenic marginal zone. Surprisingly, however, the expressi on of MOMA-1, ERTR-9, and MAdCAM-1 was normal in the lymph nodes of mi ce reconstituted with LT alpha(-/-) cells. In addition, peanut aggluti nin-positive germinal centers were observed in both the spleen and mes enteric lymph nodes, although in the absence of detectable FDC. Furthe rmore, in animals reconstituted with a mixture of LT alpha(-/-) and WT c-kit(+)Lin(-)Sca(-)1(+), GC contained either predominantly LT alpha( -/-) B cells or WT B cells, These results suggest that although the fo rmation of primary follicles, FDC networks, and the splenic marginal z one are all dependent on hemopoietically derived LT alpha, germinal ce nter formation and the expression of MAdCAM-1, MOMA-1, and ERTR-9 in l ymph nodes are not, Our results also suggest that the disturbed B-T ce ll separation in LT alpha(-/-) mire is unrelated to defects in the mar ginal zone.