Repertoire of human antibodies against the polysaccharide capsule of Streptococcus pneumoniae serotype 6B

We examined the repertoire of antibodies to Streptococcus pneumoniae GB cap sular polysaccharide induced with the conventional polysaccharide vaccine i n adults at the molecular level two ways. In the first, we purified from th e sera of seven vaccinees antipneumococcal antibodies and determined their amino acid sequences. Their VH regions are mainly the products of VH3 famil y genes (candidate genes, 3-23, 3-07, 3-66, and 3-74), but the product of a VH1 family gene (candidate gene, 1-03) is occasionally used. All seven ind ividuals have small amounts of polyclonal kappa(+) antibodies (V kappa 1 to V kappa 4 families), although kappa(+) antibodies are occasionally dominat ed by antibodies formed with the product of the A27 V kappa gene. in contra st, lambda(+) anti-6B antibodies are dominated by the antibodies derived fr om one of 3 very similar V lambda 2 Family genes (candidate genes, 2c, 2e, and 2a2) and C lambda 1 gene product. The V lambda 2(+) antibodies express the 8.12 idiotype, which is expressed on anti-double-stranded-DNA antibodie s, In one case, V lambda is derived from a rarely expressed V lambda gene, 10a. In the second approach, we studied a human hybridoma (Dob1) producing anti-6B antibody. Its VH region sequence is closely related to those of the 3-15 VH gene (88% nucleotide homology) and JH4 (92% homology). Its VL regi on is homologous to the 2a2 V lambda 2 gene (91%) and J lambda 1/C lambda 1 , Taken together, the V region of human anti-6B antibodies is commonly form ed by a VH3 and a V lambda 2 family gene product.