B cell receptor repertoires identified by next-generation sequencing showed signatures associated with incomplete immune reconstitution in people living with HIV.

Incomplete immune reconstitution poses a significant challenge for anti-retroviral therapy (ART) in HIV-infected individuals. The role of B cell receptors (BCRs) in immune reconstitution, a critical aspect of the immune system, has not been well elucidated in ART-experienced people. We analyzed the BCR heavy chain repertoire in immune non-responders (INRs) and immune responders (IRs) by next-generation sequencing. The BCR repertoire of INRs was characterized by a higher proportion of longer HCDR3 and reduced frequencies of IGHV1-69, IGHJ2, and IGHV1-69/IGHJ4 and IGHV5-51/IGHJ4 pairings. INRs, rather than IRs, carried HCDR3 genes which were highly homologous to anti-HIV broadly neutralizing antibodies targeting the six-helix bundle (6HB) in envelope gp41. The plasmas of INRs also exhibited an increased reactivity to FPPR-N36, a peptide within 6HB. These findings indicated a potential association between BCR, antibodies to partial gp41, and incomplete immune reconstitution and provided new perspectives for understanding the BCR repertoire and immune reconstitution.