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. Author manuscript; available in PMC: 2013 Nov 3.
Published in final edited form as: Int Rev Immunol. 2012 Aug;31(4):10.3109/08830185.2012.703272. doi: 10.3109/08830185.2012.703272

Figure 1. Agonistic anti-CD40 MAbs require a nearby FcγR-bearing cell to cluster CD40 and induce a signal.

Figure 1

In the original Banchereau et al. B cell system, FcγR-expressing fibroblasts were needed in order for anti-CD40 antibody to stimulate B cell proliferation (30). Recent studies from three groups have shown that FcγRs, particularly FcγRIIB, are needed for anti-tumor immune effects in clinically relevant models of agonistic anti-CD40 antibodies (31-33) (drawing adapted from (32)). It has been proposed that APCs could express both CD40 and FcγRIIB so that a cis effect could occur (34) (not shown), but this was not reflected in the original Banchereau et al. B cell system in which B cells express both CD40 and FcγRIIB. Consequently, there may be spatial restrictions on where in the body agonistic anti-CD40 antibodies can exert their immune-stimulating effects. This spatial restriction would not be shared by soluble multimeric forms of CD40L which may be more effective for this reason.