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* Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands;
Trudeau Institute, Saranac Lake, NY 12983;
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; and
Department of Immunology, DNAX Research Institute, Palo Alto, CA 94304
The molecular and cellular events that initiate the formation of T and B cell areas in developing lymph nodes are poorly understood. In this study we show that formation of the lymphoid architecture in murine neonatal lymph nodes evolves through a series of distinct stages. The initial segregation of T and B cells is regulated in a CXCL13-independent manner, characterized by the localization of B cells in a ring-like pattern in the outer cortex on day 4. However, during this CXCL13-independent phase of lymph node modeling, CXCL13 is expressed and regulated in a lymphotoxin-
1
2 (LT12)-dependent manner. Surprisingly, neonatal B cells are unable to respond to this chemokine and also lack surface LT12 expression. At this time, CD45+CD4+CD3– cells are the predominant LT12-expressing cells and are also capable of responding to CXCL13. From day 4 on, architectural changes become CXCL13 dependent, and B cells become fully CXCL13 responsive, express LT12, and cluster in anatomically distinct follicles. Because the initial induction of CXCL13 is dependent on LT12, a role for CD45+CD4+CD3– cells in inducing chemokine expression in the developing lymph nodes is proposed and, as such, a role in initiation of the shaping of the microenvironment.
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