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Department of Pathology, University of Chicago, Chicago, IL 60637
The formation of germinal centers (GC) around follicular dendritic
cells (FDC) is a critical step in the humoral immune responses that
depends on the cooperative effects of B cells and T cells. Mice
deficient in either TNF or lymphotoxin (LT) fail to form both GC and
FDC network in B cell follicles. To test a potential complementary
effect of TNF and LT, a mixture of bone marrow cells from
TNF-/- mice and LT
-/- mice was
transferred into irradiated LT-/- mice or
TNF-/- mice. Interestingly, the formation of both GC and
FDC clusters in B cell follicles was restored in such chimeric mice,
suggesting that TNF and LT from different cells could complement one
another. To identify the exact contributions of each subset to the
complementary effect of TNF and LT, different sources of T and B cells
from LT-/- mice or TNF-/- mice were used
for reconstitution. Our study demonstrates that either T or B
cell-derived TNF is sufficient to restore FDC/GC in the presence of
LT-expressing B cells. However, TNF itself is not required for GC
reactions if the FDC network is already intact. Thus, the development
and maintenance of these lymphoid structures depend on a delicate
interaction between TNF and LT from different subsets of
lymphocytes.
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