Journal
JOURNAL OF IMMUNOLOGY
Volume 173, Issue 8, Pages 4889-4896Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.173.8.4889
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Funding
- NHLBI NIH HHS [HL69409] Funding Source: Medline
- NIAID NIH HHS [AI50844] Funding Source: Medline
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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-alpha(1)beta(2) (LTalpha(1)beta(2))-dependent manner. Surprisingly, neonatal B cells are unable to respond to this chemokine and also lack surface LTalpha(1)beta(2) expression. At this time, CD45(+)CD4(+)CD3(-) cells are the predominant LTalpha(1)beta(2)-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 LTalpha(1)beta(2), and cluster in anatomically distinct follicles. Because the initial induction of CXCL13 is dependent on LTalpha(1)beta(2), 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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