Cees van Kooten and Jacques Banchereau

Dept of Nephrology, Leiden University Hospital, Leiden, the Netherlands and Schering-Plough, Laboratory for Immunological Research, Dardilly, France

Received 11/14/96; Accepted 12/02/96; On-line 01/01/97

2. INTRODUCTION

12 years after the identification of the CD40 antigen through monoclonal antibodies, a wealth of information has been generated, which identify CD40 and its ligand as critical entities in the regulation of immune responses. The interest on this molecule is increasing as shown by a Medline search for the textword "CD40", which yielded 6 hits in 1989, 18 in 1990-mid1991, 71 in mid1991-1992, 110 in 1993, 210 in 1994-mid1995 and 248 in mid1995-mid1996, respectively.

Early studies, concentrated on the role of CD40 in B cell physiology, have culminated with the finding that a defective CD40-CD40-L interaction (by mutations in the CD40-L gene), is actually the cause for the X-linked immunodeficiency hyper-IgM syndrome. Since, the availability of specific molecular tools and the generation of both CD40 and CD40-L knockout mice, have extended the research in much broader ways. Recent investigations have resulted in an explosion of data concerning: 1) the structure and expression of CD40 and its ligand; 2) the signal transduction mechanisms of CD40; 3) the functional expression of CD40 on cells other than B cells; 4) the in vivo role of CD40-CD40-L interactions. As these later developments will be the focus of the present review, readers are referred to several other recent reviews (1-6).