Difference in apoptosis induction between surface IgD and IgM.
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-delta without signal 2, purified small dense B cells from untreated mice exposed to any of three monoclonal anti-delta antibodies or to polyclonal anti-delta in vitro showed modest S phase entry at 50 microg/ml. In contrast, at low doses (0.1-0.5 microg/ml) of anti-delta, there was no cell cycle entry at 64 h, but apoptosis was accelerated at 16 h. Polyclonal anti-mu and three monoclonal anti-mus did not show this early apoptosis induction. Anti-CD40 and IL-4 inhibited apoptosis in B cells treated with 0.5 microg/ml anti-delta and increased S phase entry at 10 microg/ml anti-delta. Low-dose anti-delta (but not anti-mu) 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-delta than with anti-mu, followed by an abrupt fall below baseline, a sequence previously linked to apoptosis. There was no change in Bcl-2, Bcl-x(L) or Bax. These data suggest a functional difference between delta and mu 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.
Peckham
D
D
Department of Medicine, Iowa City Veterans Administration Medical Center, Iowa City, IA 52242, USA.
Andersen-Nissen
E
E
Finkelman
F D
FD
Stunz
L L
LL
Ashman
R F
RF
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000276:immunology; D002453:Cell Cycle; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007072:Immunoglobulin D / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007152:Immunologic Capping; D015847:Interleukin-4 / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4