Sequence analysis of light chain genes from human intestinal plasma cells demonstrates that lambda genes are almost all in-frame and highly mutated and most kappa genes are highly mutated when in-frame and minimally mutated when out-of-frame.
Around 80 % of immunoglobulin (Ig)-producing cells in man are located in the gut, with a preponderance of IgA- and IgM-producing cells that express heavily mutated IgVH genes. Here we describe the characteristics of Ig light chain genes isolated from human ileal and colonic lamina propria plasma cells. We focused on the properties of the two most commonly used light chain families, Vkappa1 and Vlambda2. Out-of-frame lambda rearrangements were very rare, suggesting that these lambda light chains may have undergone sequential rearrangements until successful conformation was achieved. This has not been observed in the human peripheral B cell population. The in-frame lambda gene rearrangements were highly mutated, with a frequency of mutation that was indistinguishable from that observed in many groups of heavy chain variable regions used by intestinal plasma cells. The in-frame kappac chain rearrangements were also highly mutated, but contained a subgroup of genes (27.3 %) that showed over 98 % homology with the germ-line gene. The majority of unused kappa chain genes were unmutated. A strong tendency for preferential mutation of G over C nucleotides was observed. Detailed analysis of the sequences in which the biases were observed suggested that this was likely to be due to selection, rather than a characteristic of the mechanism introducing the mutations.
Boursier
L
L
Guy's, King's and St Thomas' Medical School, Department of Histopathology, London, GB.
Dunn-Walters
D K
DK
Spencer
J
J
D000368:Aged; D000369:Aged, 80 and over; D020816:Amino Acid Motifs / Q000235:genetics; D019943:Amino Acid Substitution; D001483:Base Sequence; D003106:Colon / Q000166:cytology / Q000276:immunology; D004252:DNA Mutational Analysis; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006801:Humans; D007082:Ileum / Q000166:cytology / Q000276:immunology; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D007146:Immunoglobulin lambda-Chains / Q000235:genetics*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010950:Plasma Cells / Q000276:immunology*; D017354:Point Mutation; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains