The immune response to type II and type VIII pneumococcal vaccines in Basilea rabbits lacking K light chains. Immunochemical and partial amino acid sequence studies of the light chains

Abstract

Twenty-four rabbits from the variant strain Basilea which lack k light chains were hyperimmunized with type II and type VIII pneumococcal vaccines. Homozygous rabbits (bas/bas) produced antibodies with λ chains, whereas heterozygotes at the L chain locus (5/bas or 9/bas) all produced antibodies with k chains. The magnitude of the response was high (antibody level: 4–40 mg/ml). The incidence of pauciclonal responses was high (2–7 major non-overlapping clonotypes) while bi- and monoclonal responses were rare, a situation very similar to that found in outbred hyperimmunized standard rabbits expressing k chains. Fragmentary amino-acid sequence data on the variable regions of the unblocked fraction of bas light chains revealed considerable structural heterogeneity at the N-terminal portion of the chains, thus suggesting the presence of several V λ subgroups, in marked contrast to the mouse λ system. Two major L chain N-terminal sequences in equal yields were identified in antibody 4826; one of the two was homologous to murine and human λ counterparts whereas the other was surprisingly similar to k chains, and in particular to b 9 N-terminal sequence. The latter could not be attributed to a k chain subgroup as the amount of b 9 molecules in antibody 4826 was less than 1% of the total antibody IgG molecules. Thus. these two sequences probably reflect the expression of 2 distinct V λ subgroups. Framework substitutions between positions 68–83 were observed in L chain 4395 as compared with λ chains from b 5 suppressed animals (Apella et al., 1974). Taken together, the results strongly suggest that in Basilea rabbits, the repertoire of V λ chain genes is large and of similar size to that of k chain genes. Partial sequence data on the C region of bas L chains clearly identify them as of λ type.