Initiation of Cellular Organization in Lymph Nodes Is Regulated by Non-B Cell-Derived Signals and Is Not Dependent on CXC Chemokine Ligand 13

  • Cupedo T
  • Lund F
  • Ngo V
  • et al.
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Abstract

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-α1β2 (LTα1β2)-dependent manner. Surprisingly, neonatal B cells are unable to respond to this chemokine and also lack surface LTα1β2 expression. At this time, CD45+CD4+CD3− cells are the predominant LTα1β2-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 LTα1β2, and cluster in anatomically distinct follicles. Because the initial induction of CXCL13 is dependent on LTα1β2, 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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Cupedo, T., Lund, F. E., Ngo, V. N., Randall, T. D., Jansen, W., Greuter, M. J., … Mebius, R. E. (2004). Initiation of Cellular Organization in Lymph Nodes Is Regulated by Non-B Cell-Derived Signals and Is Not Dependent on CXC Chemokine Ligand 13. The Journal of Immunology, 173(8), 4889–4896. https://doi.org/10.4049/jimmunol.173.8.4889

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