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Harold C. Simmons Arthritis Research Center and Departments of Internal Medicine and
Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75235
Activated B cells and T cells express CD154/CD40 ligand in vitro.
The in vivo expression and function of B cell CD154 remain unclear and
therefore were examined. Tonsillar B and T cells expressed CD154 at a
similar density both in situ and immediately ex vivo,
whereas a significantly higher percentage of the former expressed
CD154. CD154-expressing B cells were most frequent in the
CD38positiveIgD+ pre-germinal center (GC)/GC
founder, CD38positive GC and
CD38-IgD- memory populations, and were also
found in the CD38-IgD+ naive and
CD38brightIgD+ plasmablast subsets, but not in
the CD38brightIgD- plasma cell subset. B cell
expression of CD154 was induced by engaging surface Ig or CD40 by
signals that predominantly involved activation of AP-1/NF-AT and
NF-
B, respectively. The functional importance of CD154-mediated
homotypic B cell interactions in vivo was indicated by the finding that
mAb to CD154 inhibited differentiation of
CD38positiveIgD- GC B cells to
CD38-IgD- memory cells. In addition, mAb to
CD154 inhibited proliferation induced by engaging sIg or CD40,
indicating the role of up-regulation of this molecule in facilitating B
cell responsiveness. Of note, CD154 itself not only functioned as a
ligand but also as a direct signaling molecule as
anti-CD154-conjugated Sepharose beads costimulated B cell responses
induced by engaging surface Ig. These results indicate that CD154 is
expressed by human B cells in vivo and plays an important role in
mediating B cell responses.
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