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Disparity in the kinetics of onset of hypermutation in immunoglobulin heavy and light chains
Author(s) -
Van Der Keyl Harjeet,
Gellad Ziad F,
Owen Judith A
Publication year - 2000
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2000.00903.x
Subject(s) - somatic hypermutation , immunoglobulin light chain , antibody , immunoglobulin class switching , isotype , mutation frequency , germline mutation , mutation , point mutation , biology , microbiology and biotechnology , nucleotide , immunoglobulin heavy chain , immunoglobulin d , genetics , affinity maturation , heavy chain , somatic cell , gene , b cell , monoclonal antibody
The present paper describes a comparative analysis of light chains associated with primary and secondary IgM, as well as with secondary IgG antibodies to fluorescein, undertaken in order to explore the relationship between light chain somatic hypermutation and the isotype switch. The data reveal a disparity in the frequency of somatic hypermutation of secondary IgM heavy versus light chains. Among 20 secondary IgM light chains, a mutation frequency of 1/777 nucleotides was defined. In contrast, our previous analysis of the heavy chains of these molecules had identified a mutation frequency of 1/129. Among 17 IgG‐derived light chains, obtained from animals killed at the same time point as those from which the secondary IgM antibodies were obtained, we measured a mutation frequency of 1/77. Finally, analysis of 20 light chains derived from primary IgM antibodies revealed a mutation frequency of only 1/1192 nucleotides. These data demonstrate that, prior to the class switch, light chain mutation occurs at a frequency considerably lower than that measured for the associated heavy chain gene. Six additional apparent mutations in the secondary IgM antibody 95B3 were all shared with a set of IgG antifluorescein antibodies belonging to the Vκ 34 family. It is suggested that these light chains represent the products of a previously uncharacterized germ line gene.