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

Journal article
Authors Alaitz Aranburu
Nina Höök
Natalija Gerasimcik
Bjorn Corleis
Weicheng Ren
Alessandro Camponeschi
Hans Carlsten
Ola Grimsholm
Inga-Lill Mårtensson
Published in European Journal of Immunology
Volume 48
Issue 3
Pages 509-521
ISSN 0014-2980
Publication year 2018
Published at Institute of Medicine, Department of Rheumatology and Inflammation Research
Pages 509-521
Language en
Keywords Autoimmunity, CD21 B cells −/low, H-CDR3 repertoire, Memory B cells, SLE animal model
Subject categories Immunobiology

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 exhib its 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 V H 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.

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