The Strength of B Cell Interaction with Antigen Determines the Degree of IgM Polymerization

Abstract

The induction of variable disulfide polymerization of IgM in the trout (Oncorhynchus mykiss) and its effect on its half-life were examined. An association between greater Ab affinity and increased disulfide polymerization was first indicated by the observation of this increased IgM disulfide polymerization during the process of affinity maturation. A direct association between Ab affinity and disulfide polymerization was then established by the fractionation of individual sera into high- and low-affinity subpopulations, which also resulted in the partitioning of high and low degrees of disulfide polymerization. The ability of high-affinity B cells to produce more highly polymerized Abs upon Ag induction was demonstrated by in vitro Ag-driven selection. Low Ag concentrations, which elicited only high-affinity Abs, also possessed the highest degree of polymerization, whereas higher concentrations of Ag elicited a broader array of Ab affinities, yielding a lower average affinity and degree of polymerization. Half-life studies revealed that the high-affinity, highly polymerized Abs possessed longer half-lives than the lower-affinity, lightly polymerized Abs. Finally, although the affinity for Ag is associated with elevated levels of polymerization, analysis of naive Ig revealed that the degree of polymerization alone, not affinity, appears sufficient to prolong Ig half-life.

Differential compartmentalization of memory B cells versus plasma cells in salmonid fish

“…First, the kinetics, magnitude, and affinity of the TI and TD responses were quite similar. Both responses exhibited a relatively short primary phase versus a prolonged secondary and both maintained the high affinity achieved late in the primary (by week 16), even as the titers began to wane (week [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44]. This heightened affinity continued into the secondary, with even a slight increase (∼from −log aK 5.9 to 6.2), late in the secondary.…”

“…However, precise quantitative comparisons between antibody titers and ASCs cannot be made as (i) the secretion rate of the ASCs (composed of PCs and plasmablasts) increases over time postimmunization [41], and (ii) high-affinity antibodies, which dominate the late immune response [20], possess more prolonged half-lives [42,43] thus making such comparisons problematic. Indeed, based on these previous studies [41][42][43], one should expect that fewer ASCs would give rise to higher antibody titers as the response matures.Two features of these antibody responses; however, were particularly notable. First, the kinetics, magnitude, and affinity of the TI and TD responses were quite similar.…”

The differential dynamics of antibody subpopulation expression during affinity maturation in a teleost

“…For example this limited persistence could be a reflection of the relatively shorter half-life of low affinity antibodies [35], or the limited persistence of the responsible antibody secreting cells. High rates of secretion are typically seen in the murine plasma cell, while the plasmablast typically possesses much lower secretion rates and appears primarily early in the response [36,37].…”

Polyclonal hypergammaglobulinemia and autoantibody production induced by vaccination in farmed Atlantic salmon

“…Salmon lack the germinal center and IgM class switching to IgG [24]. Nevertheless, it has been shown that affinity maturation does occur in teleost [25,26]. In human and murine autoimmune diseases, formation of ectopic lymphoid structures in inflamed tissues has been associated with autoantibody production and autoimmune disease [27].…”