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Transfer of Primitive Stem/Progenitor Bone Marrow Cells from LT^-/- Donors to Wild-Type Hosts: Implications for the Generation of Architectural Events in Lymphoid B Cell Domains¹

Reina E. Mebius^2,3,*, Silvy van Tuijl^*, Irving L. Weissman^, and Troy D. Randall^2,§

^* Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands; Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305; and ^§ Trudeau Institute, Saranac Lake, NY 12983

To analyze whether the phenotypic abnormalities observed in lymphotoxin-^-/- (LT^-/-) mice are intrinsic to the hemolymphoid system itself or dependent on stromal elements, wild-type (WT) mice were reconstituted with bone marrow (BM) cells enriched for hemopoietic stem cells from LT^-/- animals. WT mice reconstituted with LT^-/-c-kit⁺Lin^-Sca-1⁺ BM cells do not maintain follicular dendritic cell (FDC) networks and do not form primary follicles, while clear 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 absent from the splenic marginal zone. Surprisingly, however, the expression of MOMA-1, ERTR-9, and MAdCAM-1 was normal in the lymph nodes of mice reconstituted with LT^-/- cells. In addition, peanut agglutinin-positive germinal centers were observed in both the spleen and mesenteric lymph nodes, although in the absence of detectable FDC. Furthermore, in animals reconstituted with a mixture of LT^-/- and WT c-kit⁺Lin^-Sca-1⁺, GC contained either predominantly LT^-/- B cells or WT B cells. These results suggest that although the formation of primary follicles, FDC networks, and the splenic marginal zone are all dependent on hemopoietically derived LT, germinal center formation and the expression of MAdCAM-1, MOMA-1, and ERTR-9 in lymph nodes are not. Our results also suggest that the disturbed B-T cell separation in LT^-/- mice is unrelated to defects in the marginal zone.

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