© The Rockefeller University Press, 0022-1007/1998/4/997/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 7, April 6, 1998 997-1007
The Sequential Role of Lymphotoxin and B Cells in the Development of Splenic Follicles
Mercedes Gonzalez*,
Fabienne Mackay
,
Jeffrey L. Browning
,
Marie H. Kosco-Vilbois
, and
Randolph J. Noelle*
From the * Department of Microbiology, Dartmouth Medical School, Lebanon, New Hampshire 03756; the
Department of Immunology, Inflammation and Cell Biology, Biogen, Cambridge, Massachusetts 02142; and the
Serono Pharmaceutical Research Institute, CH-1228 Plan-les-Ouates, Geneva, Switzerland
The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT-β receptor (LT-βR), since blocking ligand–receptor interaction in recipient SCID mice ablates the capacity of the transferred cells to segregate. A week after lymphocyte transfer, host-derived FDCs appeared in the reconstituted SCID mice. This induction of FDCs is dependent on LT-βR signaling by B cells since LT-
–/– B cells are incapable of inducing development of FDCs in SCID mice, even after cotransfer of LT-
+/+ T cells. Therefore, LT plays at least two discrete roles in splenic organization. First, it appears that LT induces the differentiation of the white pulp to create sites for lymphocyte segregation. Second, LT expression by B cells drives the maturation of FDCs and the organization of B cell follicles.
Address correspondence to Randolph J. Noelle, Department of Microbiology, Dartmouth Medical School, 1 Medical Center Dr., Lebanon, NH 03756. Phone: 603-650-7670; Fax: 603-650-6223; E-mail: rjn{at}dartmouth.edu
1Abbreviations used in this paper: CD, cluster of differentiation; FDC, follicular dendritic cell; IDC, interdigitating dendritic cell; LT, lymphotoxin; PALS, periarteriolar lymphocyte sheath.
Confocal microscopy was done at Dartmouth Medical School in The Herbert C. Englert Cell Analysis Laboratory, which was established by a grant from the Fannie E. Rippel Foundation and is supported in part by the Core grant of the Norris Cotton Cancer Center (CA 23108). This work was supported by grants from the National Institutes of Health (AI-26296 and AI-37075) to R.J. Noelle.

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