The complement system is a component of the immune system and is a series of over 20 specialized proteins that help antibodies and phagocytes to eliminate pathogens via disruption of the pathogen cell membrane. The lack of specific complements (C1q, C2, C3, and C4) or complement receptors (CR1 and CR2) causes critically diminished antibody responses. Studies have shown that the CR1 and 2 receptors are mainly expressed on B cells and follicular dendritic cells (which are located in B cell follicles of secondary lymphoid organs).
IgG3 is a subclass of IgG (immunoglobin G) and can upregulate antibody responses by way of complement. Administering IgG3 causes antigen to localize to B cell follicles in the spleen and binding of the antigen to B cells in the marginal zone (interface between the non-lymphoid and lymphoid areas of the spleen). Since previous studies have shown that IgG3-antigen complexes co-localize with follicular dendritic cells, scientists set out to study the role of IgG3 in the deposition of antigen on follicular dendritic cells and the contribution of C1q and C3 in this process.
Importance of Complement in Antibody-Antigen Binding to B Cells
Wild type and knockout mice lacking C1q and C3 were administered a biotinylated test antigen, biotin-OVA-2,4,6-trinitrophenyl (biotin-OVA-TNP) with or without IgG3 anti-TNP. Flow cytometry of splenic cells showed that IgG3 increased antigen binding to B cells of wild type mice, but not in the B cells of the knockout mice. When mice were immunized with antigen only, low levels of antigen were detected via confocal microscopy in the follicles in the knockout mice. The antigen remained in the marginal zone of the complement-deficient knockout mice. However, significant levels were found in the follicles of wild type mice. When IgG3 was co-administered with the OVA-TNP antigen in wild type mice, antibody production was enhanced, but production was reduced in the C1q and C3 knockout mice. Therefore, complement is essential in the IgG3-mediated increase in antibody production. This relevant information and the knowledge that IgG3 is associated with autoimmune diseases may contribute to a better understanding of the role of IgG3 function during infections and autoimmune diseases.
Zhang, L., Ding, Z., & Heyman, B. (2017). IgG3-antigen complexes are deposited on follicular dendritic cells in the presence of C1q and C3. Scientific Reports, 7(1). doi:10.1038/s41598-017-05704-3