Pedrioli, A. | bioRxiv Science

bioRxiv2020

Mouse-specific but infection-unspecific IgM repertoire fingerprint following viral infection

Antibody repertoire sequencing provides a molecular fingerprint of current and past pathogens encountered by the immune system. Most repertoire studies in humans require measuring the B cell response in the blood, resulting in a large bias to the IgM isotype. The extent to which the circulating IgM antibody repertoire correlates to lymphoid tissue-resident B cells in the setting of viral infection remains largely uncharacterized. Therefore, we compared the IgM repertoires from both blood and bone marrow (BM) plasma cells (PCs) following acute or chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. Despite previously reported serum alterations between acute and chronic infection, IgM repertoire signatures based on clonal diversity metrics, public clones, network and phylogenetic analysis were largely unable to distinguish infection cohorts. Our findings, however, revealed mouse-specific congruence between the blood and PC repertoires irrespective of infection status. Our study reveals that IgM repertoire analyses may be unsuitable for providing a fingerprint of current or previous immune challenges.

immunology↗

bioRxiv2020

Profiling virus-specific Tcf1+ T cell repertoires during acute and chronic viral infection

CD8 T cells play a crucial role in providing protection from viral infections. It has recently been established that a subset of CD8 T cells expressing Tcf1 are responsible for sustaining exhausted T cells during chronic lymphocytic choriomeningitis virus (LCMV) infection. Many of these studies, however, have been performed using T cell receptor (TCR) transgenic mice, in which CD8 T cells express a monoclonal TCR specific for the LCMV glycoprotein. To investigate whether the Tcf1+ and Tcf1-repertoires are naturally composed of similar or different clones in wild-type mice exposed to acute or chronic LCMV infection, we performed TCR repertoire sequencing of virus-specific CD8 T cells, including Tcf1+ and Tcf1-populations. Our analysis revealed that the Tcf1+ TCR repertoire is maintained at an equal or higher degree of clonal diversity despite harboring fewer cells. Additionally, within the same animal, there was extensive clonal overlap between the Tcf1+ and Tcf1-repertoires in both chronic and acute LCMV infection. We could further detect these virus-specific clones in longitudinal blood samples earlier in the infection. With respect to common repertoire parameters (clonal overlap, germline gene usage, and clonal expansion), we found minor differences between the virus-specific TCR repertoire of acute and chronic LCMV infection 40 days post infection. Overall, our results indicate that the Tcf1+ population emerging during chronic LCMV infection is not clonally distinct from the Tcf1-population, supporting the notion that the Tcf1+ pool is indeed a fuel for the more exhausted Tcf1-population within the heterogenous repertoire of LCMV-specific CD8 T cells.

immunology↗