A single VH gene segment encodes the immune response to phosphorylcholine: Somatic mutation is correlated with the class of the antibody

Stephen Crews, Johanna Griffin, Henry Huang, Kathryn Calame, Leroy Hood

Research output: Contribution to journalArticlepeer-review

370 Scopus citations


The immune response in BALB/c mice to phosphorylcholine is highly restricted in its heterogeneity. Of the 19 immunoglobulins binding phosphorylcholine for which complete VH-segment amino acid sequences have been determined, 10 employ a single sequence, denoted T15 after the prototype VH sequence of this group of antibodies. The remaining 9 of these VH segments are variants differing by 1 to 8 residues from the T15 sequence. Using a cloned VH cDNA probe complementary to the T15 sequence, we isolated from a mouse sperm genomic library clones corresponding to four VH gene segments that by DNA sequence analysis are >85% homologous to one another. These four VH gene segments have been denoted the T15 VH gene family. These VH gene segments are most, if not all, of the germline VH gene segments that could encode the VH sequences of antibodies that bind phosphorylcholine. One of these four genes contains the T15-VH-coding sequence. When the T15-family VH gene segments were compared with the complete VH protein sequences of 19 hybridoma and myeloma immunoglobulins that bind phosphorylcholine, several striking conclusions could be drawn. First, all of these VH regions must have arisen from the germline T15 VH gene segment. Thus virtually the entire immune response to phosphorylcholine is derived from a single VH-coding sequence. Nine of the 19 VH regions were variants differing from the T15-VH-coding sequence and, accordingly, must have arisen by a mechanism of somatic diversification. Second, the variants appear to be generated by a somatic mutation mechanism. They cannot be explained by recombination or gene conversion among members of the T15 gene family. Third, somatic mutation is correlated with the class of the antibody. All of the somatic variation is found in the VH regions derived from antibodies of the IgA and IgG classes. The IgM molecules express the germline T15 VH gene segment exclusively.

Original languageEnglish
Pages (from-to)59-66
Number of pages8
Issue number1
StatePublished - Jul 1981


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