Cross-linking the murine heat-stable antigen induces apoptosis in B cell precursors and suppresses the anti-CD40-induced proliferation of mature resting B lymphocytes.
The murine heat-stable antigen (HSA) is a glycosyl-phosphatidylinositol-linked cell surface protein which has been implicated in cellular adhesion processes, the co-stimulation of CD4+ T cells, and B cell memory. We have recently demonstrated a significant reduction in pro-B and pre-B lymphocytes in transgenic mice that overexpress HSA. We now report that cross-linking HSA with the M1/69 monoclonal antibody induces the apoptosis of cultured B cell precursors in a stomal cell and cytokine-independent manner and that sensitivity to HSA-mediated cell death increases with developmental maturity. The cross-linking of HSA does not induce apoptosis in mature splenic B cells, but instead inhibits their ability to proliferate in response to anti-CD40 + IL-4. Taken together, these data implicate HSA as a potent negative regulator of B cell development and activation.
Chappel
M S
MS
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver.
Hough
M R
MR
Mittel
A
A
Takei
F
F
Kay
R
R
Humphries
R K
RK
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D051927:CD24 Antigen; D019013:CD40 Antigens / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D002999:Clone Cells; D003432:Cross-Linking Reagents; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015851:Interleukin-7 / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051927:CD24 Antigen; D019013:CD40 Antigens; C497890:Cd24a protein, mouse; D003432:Cross-Linking Reagents; D015851:Interleukin-7; D008562:Membrane Glycoproteins