Fortifying B cells with CD154: an engaging tale of many hues

Although the original antibody to what is now defined as CD40 was raised against and shown to react with bladder carcinoma cells, the major insights into the functional attributes of this important receptor molecule - now known to be found on a diverse range of cell types - have arisen from studies on B lymphocytes. This 50 000 MW glycoprotein member of the tumour necrosis factor receptor (TNF-R) family, expressed constitutively at high density throughout B-cell differentiation, provides the focus for T-cell delivered cognate help to the B cell via the capacity to engage its inducible counterstructure - CD154; or `CD40 ligand' (CD40L). The aim of this article is to review the multiple stages at which the cognate CD40-CD40L pairing might serve to direct and modify the B-cell response with a focus on data generated from human in vitro studies set within an in vivo context gleaned primarily from observations in the mouse. The consequences of engaging CD40 on lymphoma B cells are discussed while, finally, we address how the quantity and quality of the CD154 being offered to its receptor may dictate the functional outcome of the cell in question.