The interaction between human monocytes and red cells. Specificity for IgG subclasses and IgG fragments

Area of Science:

• Immunology
• Cell Biology

Background:

• Immunoglobulin G (IgG) subclasses play diverse roles in immune responses.
• Mononuclear cells, including monocytes and lymphocytes, are crucial for cellular immunity.
• Understanding receptor-ligand interactions is vital for immune system function.

Purpose of the Study:

• To characterize the specificity of different IgG subclasses and their fragments for rosette formation with human mononuclear cells.
• To identify the specific regions of IgG responsible for binding to mononuclear cells.
• To investigate the role of disulfide bonds in IgG-Fc mediated cell binding.

Main Methods:

• Rosette formation assays using red blood cells coated with anti-D antibodies and various IgG subclasses/fragments.
• Inhibition assays with free IgG subclasses, Fc fragments, F(ab')(2), and Fab fragments.
• Chromic chloride method for specific coating of red cells with IgG subclasses.
• Analysis of inhibitory capacity after disulfide bond cleavage.

Main Results:

• Rosette formation was significantly inhibited by free Immunoglobulin G subclass 1 (IgG1) and Immunoglobulin G subclass 3 (IgG3).
• Mononuclear cells, specifically monocytes, bound to red cells coated with IgG1 and IgG3.
• The Fc fragment of IgG globulin, but not F(ab')(2) or Fab, inhibited rosette formation, indicating the Fc region's importance.
• Cleavage of disulfide bonds in Fc fragments abolished their inhibitory capacity.
• No specific receptor for C3 was confirmed on mononuclear cells in this context.

Conclusions:

• The mononuclear cell receptor exhibits specificity for Immunoglobulin G subclass 1 (IgG1) and Immunoglobulin G subclass 3 (IgG3).
• The N-terminal portion of the Fc fragment of IgG is involved in binding to mononuclear cells.
• The integrity of the inter-heavy chain disulfide bond within the Fc fragment is essential for this interaction.