Anti-phosphorylcholine antibodies of the T15 idiotype are optimally protective against Streptococcus pneumoniae.

Abstract

In the mouse, most anti-PC antibody is found in one of the three murine anti-PC idiotype families: T15, M603, or M511. The antibodies within each of these idiotypic families have characteristic fine specificities for phosphorylcholine (PC)-analogues. In this paper we compare the ability of hybridoma IgM anti-PC antibodies of the three idiotype families to protect mice from fatal infection with S. pneumoniae. Antibody bearing the T15 idiotype was approximately 8 times as effective as antibody with the M603 idiotype and approximately 30 times as protective as antibody with the M511 idiotype. Reports by others have shown that the heavy chains of virtually all mouse anti-PC antibodies are produced by translocation of a single variable region gene and that the direct translation of this gene (in the absence of somatic mutations) results in heavy chains characteristic of the T15 idiotype. Thus, our findings suggest that the T15 germ line heavy chain variable region gene may have been selected through evolution to code for antibody binding PC-containing pathogens such as S. pneumoniae. Our observations may also explain the existence of regulatory mechanisms that result in maintenance of T15 idiotype expression in murine anti-PC immune responses.

The Virulence Function of Streptococcus pneumoniae Surface Protein A Involves Inhibition of Complement Activation and Impairment of Complement Receptor-Mediated Protection

“…A capsular type 3 pneumococcal strain (WU2, PspA ϩ ) (24,25) and its isogenic mutant (JY1119, PspA Ϫ ) (4,7,26) were used. Bacterial stocks were frozen at Ϫ80°C in Todd-Hewitt broth supplemented with 0.5% yeast extract containing 10% glycerol.…”

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

“…Genetic analysis indicated that EO6, the prototypic IgM anti-OxLDL antibody, was a natural antibody secreted by innate B-1 cells in a T cell-independent (TI) manner and possessed the germline-encoded T15 clonotype (8). T15 antibodies have previously been shown to recognize the PC moiety (10), which is an immunodominant component of the cell wall of many microbes, such as Streptococcus pneumoniae (11). Our previous studies show that T15/EO6 also recognizes the PC moiety of oxidized phospholipids, as present on OxLDL and apoptotic cells, but does not recognize native PC-containing unoxidized phospholipids, as found on native LDL or viable cells (8).…”

Polyamine biosynthesis and transport mechanisms are crucial for fitness and pathogenesis of Streptococcus pneumoniae

“…The institutional animal care and use committee approved all animal studies. All experiments were performed with 8-to 12-week-old CBA/N mice (Jackson Laboratory) (Briles et al, 1982). Pneumococci were grown at 37 uC in 5% CO 2 in THY medium.…”