International Immunology, Vol 10, 1673-1682, Copyright © 1998 by Oxford University Press
RA Sater, PC Sandel and JG Monroe
Self-reactive immature B cells may be eliminated in the bone marrow (BM)
after B cell receptor (BCR) engagement in a process known as negative
selection. Immature B cells emigrating from the BM, the so- called
transitional cells, remain sensitive to negative selection and are likely
to be important targets of tolerance towards peripheral antigens.
Transitional cells are deleted through apoptosis after BCR cross-linking in
vitro. Using anti-Ig as a surrogate antigen, we determined the signaling
requirements for the induction of apoptosis in transitional cells.
Treatment with anti-Ig for only 20 min causes most cells to be apoptotic 16
h later. Furthermore, apoptosis of transitional cells is induced with low
doses of anti-Ig while mature cell proliferation requires extended culture
at 30-fold higher concentrations. For both populations of B cells, total
surface Ig expression is equivalent, therefore indicating that the
threshold of BCR signaling required to elicit these responses is different.
T cell help can modulate B cell tolerance. However, specific help may not
be available when apoptosis is triggered by a peripheral antigen. The
opportunity to reverse apoptosis of transitional cells is surprisingly
long. Even 8 h after anti-Ig treatment, IL-4 or anti-CD40 antibody can
block apoptosis. The upper time limit of protection is concurrent with
irreversibility of apoptosis as measured by DNA fragmentation. These
findings indicate that B cell negative selection is more easily triggered
than activation, and that the induction of apoptosis and its reversal by T
cell help can be events that occur in distinct microenvironments.
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B cell receptor-induced apoptosis in primary transitional murine B cells: signaling requirements and modulation by T cell help [In Process Citation]
Department of Neurology, University of Pennsylvania, Philadelphia 19104, USA.
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