Requirement for complement in antibody responses is not explained by the classic pathway activator IgM

Area of Science:

• Immunology
• Complement System
• Antibody Production

Background:

• The classic complement pathway is vital for adaptive immunity, primarily initiated by antigen-antibody complexes.
• Its role in primary antibody responses is unclear, as specific antibodies are scarce in naive individuals.
• A hypothesis suggested IgM from naive mice might initiate this pathway.

Purpose of the Study:

• To investigate the role of IgM-mediated complement activation in primary antibody responses.
• To determine if IgM's ability to activate complement is essential for normal antibody production.

Main Methods:

• Generated a knock-in mouse strain (Cμ13) with non-complement-activating IgM.
• Assessed antibody responses to sheep erythrocytes and keyhole limpet hemocyanin in Cμ13 mice.
• Examined antibody responses in mice lacking other classic pathway activators (SCRM1, SAP, CRP).

Main Results:

• Cμ13 mice exhibited normal antibody responses, similar to wild-type mice.
• Antibody production remained unaffected in mice lacking SCRM1, SAP, or CRP.
• These findings indicate IgM does not require complement activation for primary antibody responses.

Conclusions:

• Secreted IgM and classic pathway activation are necessary for primary antibody responses, but IgM-mediated complement activation is not.
• The classic pathway can be initiated independently of IgM's complement-activating ability.
• Other endogenous activators of the classic pathway are also not essential for normal primary antibody responses.