Mouse monoclonal antibodies to pneumococcal C-polysaccharide backbone show restricted usage of VH-DH-JH gene segments and share the same kappa chain

The immunization of BALB/c mice with heat-killed cells of Streptococcus mitis SK598 allowed the rescue of mouse monoclonal antibodies (mAbs) reactive with the pneumococcal cell wall C-polysaccharide backbone. We report for the first time the genetic and molecular characterization of these mAbs, which altogether reflect a typical thymus-independent type 2 immune response. They were isotype-diverse (IgM, IgG1, IgG2b and IgG3). They made use of restricted and scarcely mutated VH-DH-JH combinations, and the same kappa chain, essentially in germ line configuration. Interestingly, this light chain was also found making up part of an anti-phosphorylcholine mAb. These mAbs were not inhibited by phosphorylcholine and related compounds, nor N-acetylneuraminic acid (NANA), nor the Forssman disaccharide; some of them showed limited reactivity with the meningococcal C polysaccharide. Their CDR-H3s do not show any recognizable patterns resembling those found in antibodies to bacterial polysaccharides that have already been characterized.