How antibodies use complement to regulate antibody responses.

Area of Science:

• Immunology
• Complement System
• Antibody Regulation

Background:

• Antibodies binding antigens form immune complexes that can modulate antibody responses.
• Immune complexes, especially those with IgM and IgG, activate the complement system.
• Complement components can become part of immune complexes, influencing immune responses.

Purpose of the Study:

• To review experimental data on how antibodies upregulate specific antibody responses via the complement system.
• To elucidate the mechanisms by which different antibody isotypes interact with complement.
• To discuss the role of complement in antibody responses to both complexed and free antigens.

Main Methods:

• Review of existing experimental data on antibody-antigen interactions and complement activation.
• Analysis of studies involving different murine IgG isotypes (IgG1, IgG2a, IgG2b, IgM, IgG3).
• Examination of data from experiments using knockout models lacking complement components (C1q, Factor B, MBL) and complement receptors (CR1/2).

Main Results:

• Murine IgG1, IgG2a, and IgG2b primarily upregulate antibody responses via Fc-receptors, not complement.
• IgM and IgG3 antibodies enhance antibody responses through the complement system, requiring complement receptors 1 and 2 (CR1/2).
• Lack of C1q significantly impairs antibody responses, suggesting the classical complement pathway's involvement, while Factor B or MBL deficiency has less impact.

Conclusions:

• The complement system is critical for antibody responses, particularly for IgM and IgG3, which utilize complement receptors.
• While C1q is essential, the precise role of other classical pathway activators in vivo remains unclear.
• Further investigation is needed to explain normal antibody responses in mice lacking certain classical pathway activators.