A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE

Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Clinical Immunology (Impact Factor: 3.67). 03/2008; 126(2):189-201. DOI: 10.1016/j.clim.2007.10.004
Source: PubMed


We previously reported that some systemic lupus erythematosus (SLE) patients have a population of circulating memory B cells with >2-fold higher levels of CD19. We show here that the presence of CD19(hi) B cells correlates with long-term adverse outcomes. These B cells do not appear anergic, as they exhibit high basal levels of phosphorylated Syk and ERK1/2, signal transduce in response to BCR crosslinking, and can become plasma cells (PCs) in vitro. Autoreactive anti-Smith (Sm) B cells are enriched in this population and the degree of enrichment correlates with the log of the serum anti-Sm titer, arguing that they undergo clonal expansion before PC differentiation. PC differentiation may occur at sites of inflammation, as CD19(hi) B cells have elevated CXCR3 levels and chemotax in response to its ligand CXCL9. Thus, CD19(hi) B cells are precursors to anti-self PCs, and identify an SLE patient subset likely to experience poor clinical outcomes.

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Available from: Mary Anne Dooley, Mar 17, 2014
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    • "B cells from lupus patients are known to be hyperresponsive to stimulation through the BCR as evidenced by increased LYN and ERK1/2 phosphorylation [19], [31]. However, it was initially unclear if the same differences would be observed in EBV transformed B cell lines from lupus patients compared to B cell lines derived from unaffected controls. "
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    • "The MAPK pathway was also highlighted in network analysis. Nicholas et al. [44] demonstrated that CD19hi B cells had increased basal levels of phosphorylated Syk and ERK1,2. Similarly, B prosurvival signaling required sustained activation of Akt and ERK kinases which were associated with elevated anti-apoptotic proteins Mcl-1, Bcl-xL and XIAP [45]. "
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    • "Additional studies have characterized a population of CD19high-expressing B cells in patients with SLE and ANCA-associated vasculitis, representing up to 10% of the B cells in most patients and up to 30% in individual cases [79,88,89]. CD19high B cells showed markedly higher CD19 expression than B cells from healthy controls, while the remaining CD19low B cells recapitulated the reduced CD19 expression [79] as also documented by other studies [73,80,81]. "
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