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 hea vily mutated IgV(H) genes. Here we describe the characteristics of Ig light chain genes isolated from human ileal and colonic lamina propria plasma ce lls. We focused on the properties of the two most commonly used light chain families, V(kappa)1 and V(lambda)2. Out-of-frame lambda rearrangements wer e very rare, suggesting that these lambda light chains may have undergone s equential rearrangements until successful conformation was achieved. This h as not been observed in the human peripheral B cell population. The in-fram e lambda gene rearrangements were highly mutated, with a frequency of mutat ion that was indistinguishable from that observed in many groups of heavy c hain variable regions used by intestinal plasma cells. The in-frame kappa c hain rearrangements were also highly mutated, but contained a subgroup of g enes (27.3%) that showed over 98% homology with the germ-line gene. The maj ority of unused kappa chain genes were unmutated. A strong tendency for pre ferential mutation of G over C nucleo tides 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 mechani sm introducing the mutations.