Activation of mouse complement by different classes of mouse antibody

Area of Science:

• Immunology
• Complement System Biology

Background:

• Antibodies play a crucial role in the immune response by initiating complement system activation.
• Different antibody isotypes (IgM, IgG, IgA) possess distinct effector functions, including complement fixation.

Purpose of the Study:

• To investigate the capacity of mouse anti-dinitrophenyl (DNP) antibodies of different isotypes (IgM, IgG1, IgG2, IgA) to activate complement.
• To compare complement activation by mouse antibodies using both mouse and guinea-pig complement systems.

Main Methods:

• Sensitive hemolytic assay to detect complement-mediated cell lysis.
• Two-dimensional immunoelectrophoresis to identify cleavage of mouse complement component C3.

Main Results:

• Mouse IgM anti-DNP antibodies efficiently lysed erythrocytes with guinea-pig complement but showed poor activation of mouse complement.
• A mouse IgG1 anti-DNP antibody activated mouse C3 via the alternative pathway without causing hemolysis.
• Mouse IgA myeloma proteins exhibited similar complement activation properties to IgG1.
• A mouse IgG2 anti-DNP antibody fraction demonstrated hemolysis with both mouse and guinea-pig complement, activating both classical and alternative pathways of mouse complement.

Conclusions:

• Mouse antibody isotypes exhibit differential abilities to activate complement, with significant variations between mouse and guinea-pig complement systems.
• IgM antibodies are potent activators of guinea-pig complement but weak activators of mouse complement.
• IgG2 antibodies are capable of activating both classical and alternative pathways of the mouse complement system.