B cell receptor light chain repertoires in health and disease.

摘要

B cell receptor BCR specificity is determined by the combination of heavy chain and light chain (L-chain), which undergo gene segment recombination to generate a large repertoire. The L-chain is unique in the ability to undergo receptor editing, a process which alters BCR through additional rearrangements at the L-chain loci. Receptor editing is though to play a prominent role in shaping the BCR repertoire because the majority of newly-formed BCRs are autoreactive. Using a novel microarray, kappa and lambda L-chain repertoires were studied in a variety of settings. Features of healthy L-chain repertoires include the following: all ten healthy repertoires had L-chains which were expressed at levels greater than 10% of the repertoire; differences in the expression level of L-chain V genes could be detected between individuals; and several L-chains V genes were not expressed in any repertoires. Systemic lupus erythematosus patient repertoires exhibited similar features, but these repertoires were more restricted and when compared with the healthy group, several L-chain V genes were differentially expressed. Changes in L-chain V gene expression were observed in a longitudinal analysis at two time-points separated by six months, and these changes are attributed to environmental effects. Aged repertoires were similar to young repertoires with regard to the level of diversity. In repertoire analysis of B cells from HIV infected patients, evidence of ongoing B cell activity could be identified. The combination of these data demonstrate that there is selection on L-chains during development and that changes in repertoires may be due to environmental changes or changes in the health status of individuals.