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* Department of Immunology, University of Manitoba, Winnipeg, Canada; and
Department of Microbiology, University of Washington, Seattle, WA 98195
To define better the molecular basis for follicular dendritic cell
(FDC) function, we used PCR-based cDNA subtraction to identify genes
specifically expressed in primary FDC isolated from human tonsils. In
this work we report the discovery of a novel gene encoding a small
secreted protein, which we term FDC-SP (FDC secreted protein). The
FDC-SP gene lies on chromosome 4q13 adjacent to clusters of
proline-rich salivary peptides and C-X-C chemokines. Human and mouse
FDC-SP proteins are structurally unique and contain a conserved
N-terminal charged region adjacent to the leader peptide. FDC-SP has a
very restricted tissue distribution and is expressed by activated FDCs
from tonsils and TNF-
-activated FDC-like cell lines, but not by B
cell lines, primary germinal center B cells, or anti-CD40 plus
IL-4-activated B cells. Strikingly, FDC-SP is highly expressed in
germinal center light zone, a pattern consistent with expression by
FDC. In addition, FDC-SP is expressed in leukocyte-infiltrated tonsil
crypts and by LPS- or Staphylococcus aureus Cowan strain
1-activated leukocytes, suggesting that FDC-SP can also be produced in
response to innate immunity signals. We provide evidence that FDC-SP is
posttranslationally modified and secreted and can bind to the surface
of B lymphoma cells, but not T lymphoma cells, consistent with a
function as a secreted mediator acting upon B cells. Furthermore, we
find that binding of FDC-SP to primary human B cells is markedly
enhanced upon activation with the T-dependent activation signals such
as anti-CD40 plus IL-4. Together our data identify FDC-SP as a
unique secreted peptide with a distinctive expression pattern within
the immune system and the ability to specifically bind to activated B
cells.
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