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 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-alpha1beta2 (LTalpha1beta2)-dependent manner. Surprisingly, neonatal B cells are unable to respond to this chemokine and also lack surface LTalpha1beta2 expression. At this time, CD45+CD4+CD3- cells are the predominant LTalpha1beta2-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 LTalpha1beta2, and cluster in anatomically distinct follicles. Because the initial induction of CXCL13 is dependent on LTalpha1beta2, 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.
Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
Tom
T
Cupedo
Frances E
FE
Lund
Vu N
VN
Ngo
Troy D
TD
Randall
Wendy
W
Jansen
Mascha J
MJ
Greuter
Rene
R
de Waal-Malefyt
Georg
G
Kraal
Jason G
JG
Cyster
Reina E
RE
Mebius
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000502:physiology*; D017252:CD3 Complex / Q000032:analysis; D015704:CD4 Antigens / Q000032:analysis; D002465:Cell Movement; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000096:biosynthesis; D019743:Chemokines, CXC / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000166:cytology*; D008233:Lymphotoxin-alpha / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000502:physiology*
D017252:CD3 Complex; D015704:CD4 Antigens; C515479:Ccl21c protein, mouse; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D008233:Lymphotoxin-alpha; D017493:Leukocyte Common Antigens