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-Dependent Spleen Microenvironment Supports the Generation of Memory B Cells and Is Required for Their Subsequent Antigen-Induced Activation1
,
Departments of
*
Laboratory Medicine/Pathology and
Internal Medicine, and
Howard Hughes Medical Institute and Center for Immunology, Washington University School of Medicine, St. Louis, MO 63110
Lymphotoxin 
-deficient (LT-/-) mice show
dramatically reduced IgG responses after either primary or secondary
immunizations with sheep red blood cells (SRBC). When splenocytes from
SRBC-primed wild-type donor mice were infused into irradiated naive
wild-type recipient mice, they generated a robust memory IgG response,
but not when infused into LT-/- recipients, indicating
that the microenvironment that develops in LT-/- mice
is incompetent to support the activation of this memory response. When
irradiated wild-type mice were reconstituted with splenocytes from
primed LT-/- donors and then challenged with the same
immunizing Ag, no memory response was observed, indicating further that
memory cells could not be generated in the LT-/-
environment. To address which lymphocyte subsets were impaired in the
LT-/- mice, we performed reconstitution experiments
using a hapten/carrier system and T cells and B cells from different
primed donors. There was no detectable defect in either the generation
or expression of memory T cells from LT-/- donors. In
contrast, B cells were not primed for memory in the microenvironment of
LT-/- mice. Additionally, primed wild-type memory B
cells could not express a memory IgG response in the
LT-/- microenvironment. Thus, splenic white pulp
structure, which depends on the expression of LT for its development
and maintenance, is needed to support the generation of memory B cells
and to permit existing memory B cells to express an isotype switched
memory Ig response following antigenic challenge.
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