Specific Blockade by CD54 and MHC II of CD40-Mediated Signaling for B Cell Proliferation and Survival

• Published in: Experimental cell research Vol. 265; no. 2; pp. 312 - 318
• Main Authors: Doyle, Iris S., Hollmann, C.Annette, Crispe, I.Nicholas, Owens, Trevor
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2001
• Subjects: adhesion molecules; Animals; apoptosis; Apoptosis - physiology; B lymphocytes; B-Lymphocytes - physiology; CD40 Antigens - metabolism; Cell Cycle - physiology; Cell Division - drug effects; Cell Division - physiology; Cell Survival - physiology; Cells, Cultured; cellular proliferation; Fas Ligand Protein; Female; Flow Cytometry; Histocompatibility Antigens Class II - metabolism; I-kappa B Proteins - metabolism; Intercellular Adhesion Molecule-1 - metabolism; Ligands; Lipopolysaccharides - pharmacology; Membrane Glycoproteins - metabolism; MHC; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; NF-κB; Signal Transduction - physiology; Spleen - cytology; NF-κB; apoptosis; MHC; B lymphocytes; adhesion molecules; cellular proliferation
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1006/excr.2001.5183

Regulation of B lymphocyte proliferation is critical to maintenance of self-tolerance, and intercellular interactions are likely to signal such regulation. Here, we show that coligation of either the adhesion molecule ICAM-1/CD54 or MHC II with CD40 inhibited cell cycle progression and promoted apoptosis of mouse splenic B cells. This resulted from specific blockade of NF-κB induction, which normally inhibits apoptosis. LPS- or B cell receptor (BCR)-induced proliferation was not inhibited by these treatments, and mAb-induced association of CD40 with other B cell surface molecules did not have these effects. Addition of BCR or IL-4 signals did not overcome the effect of ICAM-1 or MHC II on CD40-induced proliferation. FasL expression was not detected in B cell populations. These results show that MHC II and ICAM-1 specifically modulate CD40-mediated signaling, so inhibiting proliferation and preventing inhibition of apoptosis.