Figure 4. Lectin pathway in normal versus C2-deficient serum.

In this issue of the JCI, Selander et al. (7) examined the mechanism of complement activation by MBL in the setting of C2 deficiency. Lectins bind sugar moieties on target pathogens and subsequently activate complement via MASPs. In normal human sera, MASPs cleave C4 and C2 to form the C3 convertase C4b2a. Surprisingly, Selander et al. found that in human sera from individuals deficient in C4 or C2, MBL is still capable of inducing substantial C3 deposition by engagement of the alternative pathway and formation of the C3 convertase C3bBb. This bypass pathway may be functioning in individuals with acquired or naturally occurring complement deficiencies.