Equivalent responsiveness to branched polysaccharides and their dinitrophenyl conjugates in the Biozzi high and low responder lines of mice

Abstract

and low responder lines of mice biology, Wellcome Research Laboratories, BeckenhamDose response curves for two thymus-independent branched polysaccharides, levan and dextran B 1355, have been compared by direct plaque-forming cell assays in the Biozzi high (Ab/H) and low (Ab/L) responder lines of mice.In contrast with all of many other antigens so far tested, equivalent IgM responses were elicited by native levan (mol. wt. 2 x lo7), Pseudomonas levanicum vaccine and native dextran (mol. wt. 4 x lo7). Partially depolymerized levan (mol. wt. 5 x lo4 -7 x lo4) was surprisingly more immunogenic in Ab/L than in Ab/H mice. Furthermore, the tolerance threshold dose of both native and depolymerized levans was lower in the Ab/H line, the converse of previous findings with the linear polysaccharide SIII. Equivalent anti-DNP responses were obtained in the two lines when they were immunized with t h e hapten conjugated with levan, whereas conventional high/low separation was obtained when polymerized flagellin was used as carrier.It is concluded that nonspecific "high" and "low" responsiveness in Ab/H and Ab/L mice results not from a n intrinsic difference in their B cells, but from selective inyolvement of a n extrinsic regulation mechanism. Evidence which implicates divergence in antigen handling by macrophages as a primary factor, and the exceptional behavior of the branched polysaccharides in evading this difference are discussed.

Defective antigen presentation by macrophages from mice genetically selected for low antibody response

“…Thus, the different antigen handling by M@ from the two lines could reflect hyperactivity of L M@ in intracellular digestion resulting in a lower amount of membrane-bound antigen in immunogenic form. This view is supported by the observation that levan, which induces similar antibody responses in H and L mice [6], shows an equivalent degree of intracellular digestion in both lines [15].…”

“…Although H and L mice have not been found to differ in the in vivo phagocytosis of colloidal carbon or SRBC [14], other immunogens are phagocytosed more rapidly in L than in H mice. This is true not only for antigens which induce different antibody responses in H and L mice, such as keyhole limpet hemocyanin (KLH) and type 3 pneumococcal polysaccharide, but also for antigens, such as levan and dextran, which induce similar antibody responses in the two lines [6,151. These results imply that the rate of antigen phagocytosis is not a major factor in the regulation of antibody responsiveness in H and L mice.…”

Polygenic regulation of antibody synthesis to sheep erythrocytes in the mouse: a genetic analysis

“…These findings indicate that selective breeding has modified the general antibody synthesis, independent of antibody specificity. Nevertheless, similar responsiveness of HL and LL responders to two thymus-independent antigens, levan and dextran, has been reported [27].…”

<i>Trichinella spiralis</i> Infection in Animals Genetically Selected for High and Low Antibody Production

“…These mice also differed in antibody response to a variety of other im munogens, including parasite antigens [3,14]. However, no significant differences were found between HL and LL mice with respect to their antibody formation to thy mus-independent branched polysaccharide antigens [8], Furthermore, both lines were able to develop similar delayed hypersensi tivity reactions [2]. It has been suggested that the primary factor responsible for the difference in antibody production is the di vergence in antigen handling at the level of the macrophage [21].…”