Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.0907659 on April 10, 2008

Published online before print April 10, 2008
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(Journal of Leukocyte Biology. 2008;84:152-161.)
© 2008 by Society for Leukocyte Biology

Separation of splenic red and white pulp occurs before birth in a LT{alpha}β-independent manner

Mark F. R. Vondenhoff*,1, Guillaume E. Desanti{dagger},1, Tom Cupedo{ddagger}, Julien Y. Bertrand§, Ana Cumano{dagger}, Georg Kraal*, Reina E. Mebius* and Rachel Golub{dagger},2

{dagger} Unite du Développement des Lymphocytes, INSERM U668, Institut Pasteur, Paris, France;
* Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands;
{ddagger} Erasmus Medical Center, Department of Hematology, Rotterdam, The Netherlands; and
§ University of California, San Diego, La Jolla, California, USA

2Correspondence: Unite du Développement des Lymphocytes, INSERM U668, Institut Pasteur, 25, Rue du Dr Roux, 75724 Paris cedex 15, France. E-mail: rgolub{at}pasteur.fr

For the formation of lymph nodes and Peyer’s patches, lymphoid tissue inducer (LTi) cells are crucial in triggering stromal cells to recruit and retain hematopoietic cells. Although LTi cells have been observed in fetal spleen, not much is known about fetal spleen development and the role of LTi cells in this process. Here, we show that LTi cells collect in a periarteriolar manner in fetal spleen at the periphery of the white pulp anlagen. Expression of the homeostatic chemokines can be detected in stromal and endothelial cells, suggesting that LTi cells are attracted by these chemokines. As lymphotoxin (LT){alpha}1β2 can be detected on B cells but not LTi cells in neonatal spleen, starting at 4 days after birth, the earliest formation of the white pulp in fetal spleen occurs in a LT{alpha}1β2-independent manner. The postnatal development of the splenic white pulp, involving the influx of T cells, depends on LT{alpha}1β2 expressed by B cells.

Key Words: lymphoid tissue inducer cells • organogenesis • embryo • chemokines • stroma • mouse






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