Characterisation of T and B cell receptor repertoire in patients with systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity, marked clinically by multi-systemic inflammatory involvement. However, the molecular mechanism of breakdown of self-tolerance is still unclear. T cell/B cell-mediated immune disorders may play a vital role in the pathogenesis of SLE. In this context, we used a combination of multiplex-PCR, Illumina sequencing and IMGT/HighV-QUEST for a standardised analysis of the T cell receptor β-chain (TCRβ) and B cell receptor H-chain (BCR-H) repertoire of peripheral blood mononuclear cells in SLE patients compared with healthy volunteers. The results showed that there was an obvious reduction in BCR-H repertoire diversity and BCR-H CDR3 length in SLE patients. Notably, the pre-selection BCR-H CDR3s in SLE patients also displayed abnormal shortening, which suggests that early events in bone marrow B cell development and repertoire generation were abnormal in SLE patients. However, there was no obvious change of T cell repertoire in SLE patients, including repertoire diversity and CDR3 length. In addition, there was skewed usage of V genes and CDR3 sequences in SLE patients, which might be the result of physiological responses to environmental antigens or pathogens. In conclusion, our data revealed the specific changes of the TCR and BCR repertoires in SLE patients, which may provide new ideas for its prevention and treatment.