The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/3/855/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 5, March 1, 1999 855-864

Articles

Lymph Node Germinal Centers Form in the Absence of Follicular Dendritic Cell Networks

Pandelakis A. Koni* and Richard A. Flavell*,§

From the * Section of Immunobiology and § Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8011

Follicular dendritic cell networks are said to be pivotal to both the formation of germinal centers (GCs) and their functions in generating antigen-specific antibody affinity maturation and B cell memory. We report that lymphotoxin β–deficient mice form GC cell clusters in the gross anatomical location expected of GCs, despite the complete absence of follicular dendritic cell networks. Furthermore, antigen-specific GC generation was at first relatively normal, but these GCs then rapidly regressed and GC-phase antibody affinity maturation was reduced. Lymphotoxin β–deficient mice also showed substantial B cell memory in their mesenteric lymph nodes. This memory antibody response was of relatively low affinity for antigen at week 4 after challenge, but by week 10 after challenge was comparable to wild-type, indicating that affinity maturation had failed in the GC phase but developed later.

Key Words: lymphotoxin β • knockout mice • follicular dendritic cells • germinal centers • B cell memory

Address correspondence to Richard A. Flavell, Section of Immunobiology and Howard Hughes Medical Institute, 310 Cedar St., FMB412, Yale University School of Medicine, New Haven, CT 06520-8011. Phone: 203-737-2216; Fax: 203-785-7561; E-mail: richard.flavell{at}qm.yale.edu

Abbreviations used: APC, allophycocyanin; CG, chicken {gamma}-globulin; DIG, digoxigenin; FDC, follicular dendritic cell; GC, germinal center; GCDC, GC dendritic cell; Lin, lineage; LT, lymphotoxin; MLN, mesenteric lymph node; NP, (4-hydroxy-3-nitrophenyl)acetyl; PNA, peanut agglutinin.


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