How is the classical complement pathway activated?

• A. Binding of MBL to carbohydrates on pathogens
• B. C1 binds to antigen-tagged antibodies
• C. Direct binding to toxins
• D. Several complement proteins interact in plasma

Answer: (B)

Activation of the classical pathway begins when the C1 complex binds to antibody-coated targets. Specifically, C1 recognizes the Fc region of antibodies—most effectively when antibodies like IgM are bound in a pentamer or when multiple IgG molecules are clustered—on the surface of a pathogen or immune complex. This binding activates the C1r and then C1s proteases, triggering the proteolytic cascade that cleaves C4 and C2 to form the C3 convertase (C4b2a). This leads to downstream steps including C3 activation, opsonization, inflammation, and eventually formation of the membrane attack complex. The other options describe different pathways or non-specific interactions and do not reflect how the classical pathway is initiated.