Age‐associated B cells expanded in autoimmune mice are memory cells sharing H‐CDR3‐selected repertoires

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Age‐associated B cells (ABCs) represent a distinct cell population expressing low levels of CD21 (CD21−/low). The Ig repertoire expressed by ABCs in aged mice is diverse and exhibits signs of somatic hypermutation (SHM). A CD21−/low B‐cell population is expanded in autoimmune diseases, e.g. systemic lupus erythematosus, as well as in lupus‐prone NZB/W mice and in mice lacking a pre‐B cell receptor (SLC−/−). However, the nature of the CD21−/low B cells (hereafter ABCs) in autoimmunity is not well understood. Here we show that in young SLC−/− mice, the vast majority of the ABCs express memory B‐cell (MBC) markers in contrast to wild‐type controls. A similar population is present in lupus‐prone MRL mice before and at disease onset. In SLC−/− mice, a majority of the ABCs are IgM+, their VH genes have undergone SHM, show clonal diversification and clonal restriction at the H‐CDR3 level. ABC hybridomas, established from SLC−/− mice, secrete typical lupus autoantibodies, e.g. anti‐Smith antigen, and some of those that bind to DNA comprise a H‐CDR3 that is identical to previously described IgM anti‐DNA antibodies from lupus‐prone mice. Together, these results reveal that ABCs in autoimmune mice are comprised of autoreactive MBCs expressing highly restricted H‐CDR3 repertoires.
Funding Information
  • Reumatikerförbundet
  • Cancerfonden (CAN2014/886, CAN2016/0668)
  • Vetenskapsrådet
  • Svenska Sällskapet för Medicinsk Forskning
  • Barncancerfonden (PR2016‐0144)
  • Kungl. Vetenskaps- och Vitterhets-Samhället i Göteborg

This publication has 35 references indexed in Scilit: