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Eur J Immunol. 2018 Mar;48(3):509-521. doi: 10.1002/eji.201747127. Epub 2018 Jan 15.

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

Author information

1
Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
2
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
3
Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
4
B Cell Physiopathology Unit, Immunology Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.

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.

KEYWORDS:

Autoimmunity; CD21−/low B cells; H-CDR3 repertoire; Memory B cells; SLE animal model

PMID:
29266242
DOI:
10.1002/eji.201747127
[Indexed for MEDLINE]
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