Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 1995 Nov 1;182(5):1557-65.
doi: 10.1084/jem.182.5.1557.

CD40 Ligation Induces Apo-1/Fas Expression on Human B Lymphocytes and Facilitates Apoptosis Through the Apo-1/Fas Pathway

Free PMC article
Comparative Study

CD40 Ligation Induces Apo-1/Fas Expression on Human B Lymphocytes and Facilitates Apoptosis Through the Apo-1/Fas Pathway

E J Schattner et al. J Exp Med. .
Free PMC article


The Apo-1/Fas antigen (CD95) mediates programmed cell death of lymphocytes when bound by Fas ligand or anti-Apo-1/Fas antibody. In contrast, the CD40 antigen provides a potent activation and survival signal to B lymphocytes when it is engaged by its T cell ligand (CD40L, gp39) or cross-linked by anti-CD40 antibody. In this study, we use human tonsillar B cells and the Ramos Burkitt's lymphoma B cell line, which serves as a model for human germinal center B lymphocytes, to study the effectors of Apo-1/Fas expression and apoptosis of human B cells. We found that Apo-1/Fas expression was upregulated on both malignant and normal human B lymphocytes after CD40 ligation induced by (a) cognate T helper-B cell interaction mediated by microbial superantigen (SAg); (b) contact-dependent interaction with CD40L+, but not CD40L- Jurkat mutant T cell clones; and (c) monoclonal anti-CD40, but not any of a panel of control antibodies. Enhanced B cell Fas/Apo-1 expression is functionally significant. Coculture of Ramos Burkitt's lymphoma line cells with irradiated SAg-reactive CD4+ T cells with SAg or CD40L+ Jurkat T cells results in B cell apoptosis, evidenced by reduced cell viability and DNA laddering. This process is augmented by the addition of anti-Apo-1/Fas monoclonal antibody, consistent with an acquired susceptibility to Apo-1/Fas-mediated apoptosis. These data support an immunoregulatory pathway in which seemingly contradictory signals involving the B cell proliferation/survival antigen CD40, as well as the Apo-1/Fas molecule, which mediates programmed cell death of lymphocytes, are linked in the process of human B cell activation.

Similar articles

See all similar articles

Cited by 37 articles

See all "Cited by" articles


    1. J Immunol. 1987 Jul 1;139(1):313-8 - PubMed
    1. Nature. 1995 Mar 9;374(6518):163-5 - PubMed
    1. Science. 1989 May 19;244(4906):817-20 - PubMed
    1. Science. 1989 Jul 21;245(4915):301-5 - PubMed
    1. Clin Immunol Immunopathol. 1989 Oct;53(1):99-112 - PubMed

Publication types

MeSH terms