Glomerular Deposition of Immune Complexes Made with IgG2a Monoclonal Antibodies

Abstract

The factors that determine whether immune complexes (IC) are cleared safely from the circulation or are deposited in vulnerable tissues such as glomeruli are not well defined. To better understand how IC are handled, the present study examined the fate in vivo of three model IC preparations with different immunochemical characteristics. Radiolabeled IC were constructed with murine IgG1, IgG2a, or IgG3 anti-DNP mAbs bound to DNP-BSA, designated IgG1 IC, IgG2a IC, and IgG3 IC, respectively. The IC were infused i.v. into BALB/c mice, and clearance and tissue localization of the three IC probes were compared. The results indicate that the major portion of each IC preparation was cleared from the circulation by the liver. However, compared with the other two probes, IgG2a IC were preferentially deposited in the kidney. Histologic examination revealed the presence of IgG2a IC in glomeruli. The enhanced renal uptake of IgG2a IC could not be attributed solely to such characteristics as IC size, Ag/Ab ratio, Ab charge, or affinity. However, the preferential renal deposition of IgG2a IC was abrogated by complement depletion. Thus, enhanced renal uptake in normal mice was complement dependent. These data suggest that interactions between IC and the complement system can influence the propensity of IC to deposit in tissues susceptible to IC-mediated injury.

CXCR3 promotes the production of IgG1 autoantibodies but is not essential for the development of lupus nephritis in NZB/NZW mice

“…IgG2 isotypes are the most pathogenic in lupus nephritis in NZB/NZW mice (36). Immune complexes containing IgG2a antibodies have a higher propensity to deposit in the glomeruli of the kidney than those containing other isotypes (37). In the CXCR3 −/− NZB/NZW mice reported herein, total as well as anti‐dsDNA IgG2a and IgG2b antibody titers were not altered compared to those in WT NZB/NZW mice, while CXCR3 deficiency resulted in a significant decrease in IgG1 (auto)antibody titers.…”

Characteristics of Circulating Immune Complexes in HIV-Infected Patients with Different Viral Load

“…It should be noted that IgG-containing small structures predominated in patients with high VL. It is known that the elimination of the small complexes is more diffi cult process compared to the elimination of the large aggregates, so small structures are more likely to form deposits in tissues [5,14]. Long-term suppression of the viral replication sustained against the background of the antiretroviral therapy led to threefold decrease of the small CIC level.…”

“…They are formed after binding of antiviral antibodies with HIV-antigen. The pathogenic properties of CIC depend on their size determined mainly by the antigen-antibody ratio [5,8,14]. Moreover, different types of immunoglobulins form complexes with different properties [7].…”

Influence of the electric charge of the antigen and the immune complex (IC) lattice on the IC activation of human complement

“…1997). Although several other factors may be involved, the interactions between ICs and complement may influence the tendency for ICs to deposit in vulnerable tissues, leading to IC‐mediated injury (Gonzalez & Waxman 2000).…”