Germ line basis for antibody diversity: immunoglobulin VH-and CH-gene frequencies measured by DNA-RNA hybridization.

The reiteration frequency for mouse immunoglobulin V(H)-genes and C(H)-genes has been directly estimated by hybridization of purified MOPC 315 alpha-chain mRNA with a vast excess of mouse DNA. A biphasic C(o)t curve resulted. The low C(o)t transition (C(o)t(1/2) about 1.5) was interpreted as hybridization to V(H)-genes and the high C(o)t transition (C(o)t(1/2) about 10(3)) as hybridization to C(H)-genes. These values correspond to about 5000 V(H)-genes and less than 8 C(H)-genes. This germ-line content of V(H)-genes is sufficient to account for antibody diversity given a comparable set of V(L)-genes. Minimal-gene models are invalidated and there is no need to invoke somatic generators of diversity.