The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/4/1009/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 7, April 6, 1998 1009-1018

Articles

B Lymphocytes Induce the Formation of Follicular Dendritic Cell Clusters in a Lymphotoxin {alpha}–dependent Fashion

Yang-Xin Fu*, Guangming Huang§, Yang Wang{ddagger}, and David D. Chaplin{ddagger},§

From the * Department of Laboratory Medicine/Pathology, the {ddagger} Department of Internal Medicine, and the § Howard Hughes Medical Institute and Center for Immunology, Washington University School of Medicine, St. Louis, Missouri 63110

Lymphotoxin (LT){alpha} is expressed by activated T cells, especially CD4+ T helper type 1 cells, and by activated B and natural killer cells, but the functions of this molecule in vivo are incompletely defined. We have previously shown that follicular dendritic cell (FDC) clusters and germinal centers (GCs) are absent from the peripheral lymphoid tissues of LT{alpha}-deficient (LT{alpha}–/–) mice. LT{alpha}–/– mice produce high levels of antigen-specific immunoglobulin (Ig)M, but very low levels of IgG after immunization with sheep red blood cells. We show here that LT{alpha}-expressing B cells are essential for the recovery of primary, secondary, and memory humoral immune responses in LT{alpha}–/– mice. It is not necessary for T cells to express LT{alpha} to support these immune functions. Importantly, LT{alpha}-expressing B cells alone are essential and sufficient for the formation of FDC clusters. Once these clusters are formed by LT{alpha}-expressing B cells, then LT{alpha}-deficient T cells can interact with B cells to generate GCs and productive class-switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses.

Address correspondence to David D. Chaplin, Howard Hughes Medical Institute and Center for Immunology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110. Phone: 314-362-9047; Fax: 314-454-0486; E-mail: chaplin{at}im.wustl.edu

1 Abbreviations used in this paper: anti-CR, anti–complement receptor; BCR, B cell receptor; BM, bone marrow; CD40L, CD40 ligand; FDC, follicular dendritic cell; GC, germinal center; LT, lymphotoxin; PNA, peanut agglutinin; RAG, recombination activity gene; SRBC, sheep RBC.


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