The mouse immune response to streptococcal group A carbohydrate (GAC) utilizes many different gene segments from a diverse array of precursor Vh genes. The gene family number is estimated at 10 and the diversity of response in normal mice at over 200 different antibodies. The response is clonally restricted in each mouse immunized, but each mouse appears to express a different clonally homogeneous antibody in its serum in spite of genetically common background. The common denominator of similarity in these antibodies is their usage of highly homologous Vh gene segments, and identical Dh, and Jh segments. The serum response to GAC is entirely deficient in CBA/N mice which makes this an ideal system in which to investigate possible constraints on gene segment utilization. Recent evidence indicates that up to 5% of CBA/N B cells utilize the Vh-GAC gene segment(s) in their Ig rearrangements: thus, 5-10% of plasma cells are stainable by an anti-Vhgac antisera, and 5% of serum antibodies are positive for this serologic Vh marker by radioimmunoassay. This high frequency of expression of Vh gene(s) is greater than has previously been reported with any other Vh specific antisera, and provides an ideal experimental system to probe the Vh repertoire of CBA/N mice by examination of their B-cell derived hybridomas for structural constraints on combinatorial use. It is likely that a Vh-gene with such a high rate of representation in mouse B cells would probably serve redundantly as the V region for many antibodies of different binding specificity when combined with different D and J segments along with different L chains. Thus, the family of insulin (B-2--1 fructosan) binding proteins share the Vh-GAC V-gene but use different joining segments and L chains. This V-gene has only been observed in anti-carbohydrate antibodies of normal mice and its paradoxical high expression by CBA/N B cells which fail to respond to carbohydrate antigens remains unexplained.
