International Immunology, Vol. 13, No. 3, 285-295,
March 2001
© 2001 Japanese Society for Immunology
Difference in apoptosis induction between surface IgD and IgM
1 Department of Medicine, Iowa City Veterans Administration Medical Center, Iowa City, IA 52242, USA
2 University of Iowa College of Medicine, Iowa City, IA 52242, USA
3 Department of Medicine, University of Cincinnati College of Medicine and Cincinnati Veterans Administration Medical Center, Cincinnati, OH 45267, USA
Correspondence to: R. F. Ashman, Department of Medicine/Rheumatology, University of Iowa, C31-P GH, Iowa City, IA 52242 USA
In the classic `two-signal' model for B cell activation, signal 1 through the antigen receptor plus signal 2 through lymphokine receptors and CD40 leads to proliferation, but signal 1 alone leads to tolerance or anergy. In a protocol designed to deliver signal 1 in vitro with anti-
without signal 2, purified small dense B cells from untreated mice exposed to any of three monoclonal anti- antibodies or to polyclonal anti- in vitro showed modest S phase entry at 50 µg/ml. In contrast, at low doses (0.1–0.5 µg/ml) of anti-, there was no cell cycle entry at 64 h, but apoptosis was accelerated at 16 h. Polyclonal anti-µ and three monoclonal anti-µs did not show this early apoptosis induction. Anti-CD40 and IL-4 inhibited apoptosis in B cells treated with 0.5 µg/ml anti- and increased S phase entry at 10 µg/ml anti-. Low-dose anti- (but not anti-µ) induced increased B7-2 and class II MHC expression on a subset of B cells, many of which were in apoptosis. Larger transient increases in c-Myc and Egr-1 expression were seen with low-dose anti- than with anti-µ, followed by an abrupt fall below baseline, a sequence previously linked to apoptosis. There was no change in Bcl-2, Bcl-xL or Bax. These data suggest a functional difference between and µ cross-linking on resting spleen B cells. A BCR stimulus sufficient for early activation events, but insufficient for full G1 entry, may lead to apoptosis.
Keywords: anti-, apoptosis, B lymphocytes, cell cycle entry, spleen
Transmitting editor: J. Banchereau
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