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

Abstract

Age-associated B cells (ABCs) represent a distinct cell population expressing low levels of CD21 (CD21 ). The Ig repertoire expressed by ABCs in aged mice is diverse and exhibits signs of somatic hypermutation (SHM). A CD21 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 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 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.

Excessive CD11c + Tbet + B cells promote aberrant T FH differentiation and affinity-based germinal center selection in lupus

“…Their superior potency over FOB cells in priming T cells suggests that CD11c + Tbet + ABCs are antigenexperienced cells. Consistently, CD11c + Tbet + ABCs were shown to have selected BCR repertoire (79), with more somatic hypermutations than FOB cells but less than GCB cells (80). Our study also provided in vivo data supporting that CD11c + Tbet + ABC differentiation depends on TLR signaling adaptor MyD88, consistent with the previous finding that IL-21 and TLR7 stimulation cooperate to drive Tbet expression (38,39) and that CD11c + Tbet + ABCs are highly responsive to TLR7 stimulation (34,38).…”

B cell profiling in malaria reveals expansion and remodeling of CD11c+ B cell subsets

“…These results are consistent with clonal lineage analysis of B cells, which has demonstrated that atypical B cell BCR characteristics and replication history closely resemble that of resting memory B cells in both mice (41) and humans (11,42). For unswitched atypical B cells, there are less data available to suggest their potential origin.…”

Autoreactive B‐lymphocytes in SLE and RA patients: Isolation and characterisation using extractable nuclear and citrullinated antigens bound to immunobeads

“…This finding is in agreement with previous observations in SLE patients and after some infections and vaccinations . However, in RA patients, citrullinated antigen‐specific B cells displayed markers of class‐switched memory B cells , such as age associated CD21 low B cells . All together, these results indicate that the phenotype of ABLs is still unclear.…”