On the interaction of the first complement component C1 and its subunit C1q with solid-phase IgM immune complexes

Area of Science:

• Immunology
• Biochemistry

Background:

• Immunoglobulin M (IgM) is a crucial component of the innate immune system.
• The complement system, initiated by C1 complex binding to IgM, plays a vital role in immune responses.

Purpose of the Study:

• To investigate the interaction between C1 complex, C1q, and solid-phase anti-dextran IgM.
• To elucidate the conformational changes in IgM upon ligand binding and their effect on C1q fixation.

Main Methods:

• Enzyme-linked immunosorbent assay (ELISA) was employed to quantify C1q binding to immobilized IgM.
• The study utilized dextran (B 1355/S) as a specific polyvalent ligand to activate IgM.

Main Results:

• Immobilized IgM adopts a functional 'staple' conformation upon binding dextran, facilitating C1q fixation.
• C1q binding to IgM is antigen-concentration-dependent, with an estimated binding constant (K) of approximately 10(9) M-1.
• The C1 complex, including C1r2S2, exhibits distinct C1q fixation and dissociation properties compared to free C1q, suggesting altered molecular flexibility.

Conclusions:

• Dextran-induced conformational changes in IgM are essential for C1q recognition and stable binding.
• The pentameric structure of IgM and the composition of the C1 complex influence the association dynamics of C1q.
• Altered flexibility of C1q within the C1 complex likely explains the differential binding characteristics observed.