| 描述信息 |
Advancements in high-throughput sequencing (HTS) of antibody repertoires (Ig-Seq) have unprecedentedly improved our ability to characterize the antibody repertoires on a large scale. However, currently, only a few studies explored the influence of chronic HIV-1 infection on human antibody repertoires and many of them reached contradictory conclusions, possibly limited by inadequate sequencing depth and throughput. In order to better understand how HIV-1 infection would impact humoral immune system, in this study, we systematically analyzed the differences between the IgM (HIV-IgM) and IgG (HIV-IgG) heavy chain repertoires of 10 HIV-1 infected patients, as well as between the HIV-IgM repertoire and an IgM repertoire of 33 healthy donors (HH) generated in our previous study. Using Ig-Seq together with a comprehensive bioinformatic pipeline, a reservoir of 9,197,007 and 2,025,035 unique clones in HIV-IgM and HIV-IgG repertoires were obtained, respectively. Although these two antibody repertoires shared most VDJ gene arrangement patterns, the public unique clones accounted for only a negligible proportion in both libraries (HIV-IgM: 0.2%; HIV-IgG: 0.7%) and the diversity of unique clones in HIV-IgG remarkably reduced. Notably, in aspect of somatic mutation rates of CDR1 and CDR2, the HIV-IgG repertoire was higher than HIV-IgM, while the former was again higher than the HH repertoire. Besides, the average length of CDR3 region in HIV-IgM was significant longer than that in the HH repertoire, presumably caused by the great number of novel VDJ rearrangement patterns, especially a massive use of IGHJ6. Moreover, the junctional modifications were thoroughly analyzed to better understand the mechanism of varied repertoire diversity of HIV-1 infected patients. Some of the B cell clonotypes had numerous clones, and somatic variants were detected within the clonotype lineage in HIV-IgG, indicating HIV-1 neutralizing activities. The in-depth characterization of HIV-IgG and HIV-IgM repertoires enrich our knowledge in the profound effect of HIV-1 infection on human antibody repertoires and may have practical value for the discovery of therapeutic antibodies. |
