Evidence of IgG‐mediated enhancement of the antibody response in vivo without complement activation via the classical pathway

The complement (C) dependency of IgG‐mediated enhancement of the antibody response was investigated by immunizing mice with trinitrophenyl‐coupled keyhole limpet hemocyanin (TNP‐KLH) and either a C‐activating TNP‐specific monoclonal IgG_2a antibody (Hy‐1.2) or a mutant, non‐C‐activating variant of Hy‐1.2 (M12). Hy‐1.2 as well as M12 efficiently enhanced the anti‐KLH response, although Hy‐1.2 was more active. In addition, also a naturally non‐C‐activating TNP‐specific IgG₁ antibody enhanced the response to TNP‐coupled bovine serum albumin. Moreover, C‐activating IgG could enhance the antibody response in mice depleted of C3 by treatment with cobra venom factor. These findings suggest that the classical pathway of C activation is not required for IgG‐mediated enhancement.