The relationship between antibody redox structure and affinity in rainbow trout
Teleost immunoglobulin M (IgM), an 800 kDa tetramer, possesses considerable structural diversity due to the non-uniform disulfide polymerization of its halfmeric or monomeric subunits. However, to date, no plausible functional role for this diversity has been demonstrated or proposed. This research...
| Main Author: | |
|---|---|
| Format: | Others |
| Language: | English |
| Published: |
W&M ScholarWorks
2008
|
| Subjects: | |
| Online Access: | https://scholarworks.wm.edu/etd/1539616918 https://scholarworks.wm.edu/cgi/viewcontent.cgi?article=2485&context=etd |
| Summary: | Teleost immunoglobulin M (IgM), an 800 kDa tetramer, possesses considerable structural diversity due to the non-uniform disulfide polymerization of its halfmeric or monomeric subunits. However, to date, no plausible functional role for this diversity has been demonstrated or proposed. This research was, therefore, designed to investigate the possible functional role(s) for this diversity using the trout model. The possible relationship between this structural diversity and affinity was specifically addressed. The relationship between high levels of disulfide polymerization and high affinity was demonstrated by selective immunoadsorption and analysis of antibodies isolated during the process of affinity maturation. A pivotal determinative role of antigen/BCR affinity in conferring graded levels of disulfide bonding was demonstrated by the induction of high and mixed affinity antibodies from a single lymphocyte source in vitro. Additionally, transfer of immunopurified antibodies and labeled non-immune immunoglobulins revealed a direct effect of polymerization on antibody half-life, with selective removal of less polymerized Igs and/or retention of more fully polymerized Igs. Thus, this differential effect on half-life also results in an increase of average affinity, accentuating the process of affinity maturation. The converse, modulation of affinity by disulfide variation; however, could not be demonstrated. |
|---|