Transducing the affinity of antigen recognition into graded structural modifications of the antibody product (43.21)

Abstract

Abstract We have found that the affinity of B cell interaction with its cognate antigen governs the degree of post-translational modification of the IgM product in trout. Affinity-based, antigen-driven lymphocytic selection and induction by the antigen, TNP-LPS, not only induced high affinity antibodies in vitro, but these antibodies also possessed a greater degree of disulfide polymerization. Affinity purification of high affinity vs. low affinity serum antibodies also simultaneously resulted in the partitioning of highly polymerized antibodies into a high affinity fraction, while the lightly polymerized antibodies partitioned into the low affinity fraction. The in vivo functional relevance of this distinctive post-translational modification was then revealed upon the transfer of labeled antibodies to naïve animals. These latter studies demonstrated that highly polymerized antibodies possessed longer half-lives. Finally, the degree of intermonomeric disulfide polymerization occurring at the C-terminal Cys 578, appears proportional to the concentration of available mannosyl residues, ostensibly at the proximal N-linked glycosylation site to Cys 578. This latter finding suggests mechanism(s) by which polymerization and half-life can be regulated via the affinity of BCR recognition. This research was supported by NIFA (National Institute of Food and Agriculture) Grant Nos. 2002-35204-11685, 2005-01594-16271 and VIMS intramural support.