Humoral immunostimulation. IV. Role of complement

Area of Science:

• Immunology
• Cell Biology
• Complement System

Background:

• L cells treated with anti-L-cell antibody show stimulated nucleoside uptake and growth.
• Fresh, unheated sera significantly enhance this immunostimulation, suggesting the involvement of serum factors.

Purpose of the Study:

• To identify the specific factors in unheated serum responsible for enhancing immunostimulation.
• To elucidate the role of the complement system in antibody-mediated cell growth stimulation.

Main Methods:

• Utilized sera deficient in various complement components (C1r, C2, C4, C3-C9, C5, C6) to assess their role in immunostimulation.
• Investigated the effect of varying anti-serum concentrations on complement pathway involvement.
• Restored stimulation using purified complement components (C2, C3).
• Confirmed classical pathway activation by measuring complement component C4 consumption and C3 deposition on cell surfaces via immunofluorescence.

Main Results:

• At low antibody concentrations, immunostimulation required intact classical complement pathway components.
• At high antibody concentrations, both classical and alternate complement pathways contributed to enhancement.
• Complement component C3, when activated, was crucial for restoring stimulation in deficient sera.
• Deposition of human C3 on the cell surface was observed.

Conclusions:

• Complement activation, particularly through C3 via either the classical or alternate pathways, enhances L cell nucleoside incorporation and growth.
• The classical complement pathway is involved at low antibody concentrations, while both pathways are implicated at higher concentrations.
• The mechanism likely involves a direct effect of C3 on the cell membrane, though it remains to be fully elucidated.