Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that is known to be associated with polyclonal B-cell hyper-reactivity. B-cell receptor (BCR) has a central role in B-cell development, activation, survival and apoptosis, and thus is a critical component of the regulation of both protective and autoreactive B cells. In this study, we applied multiplex PCR and Illumina high-throughput sequencing to study the composition and variation of the BCRs in peripheral blood mononuclear cells from SLE patients and healthy donors (NC). We found that SLE group displayed significantly shorter CDR3 average length (14.86±0.76aa vs 15.70±0.43aa), more arginine percentage of CDR3 amino acids (7.57±0.20% vs 7.32±0.19%) and poorer immunological diversity than the healthy ones. CDR3 sequence YGMDV present in all SLE samples may provide more information in generating more effective B-cell targeted diagnosis/therapies strategies.