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: 3.99). 03/2008; 126(2):189-201. DOI: 10.1016/j.clim.2007.10.004
Source: PubMed

ABSTRACT 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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    • "In healthy individuals, CXCR3 expression on B cells is limited to a fraction of naive and memory B cells, and its expression is induced by IFN- (Jones et al., 2000; Muehlinghaus et al., 2005). However, in certain diseases, such as active SLE, a subset of CD19 high B cells enriched in autospecific Ig receptors expresses CXCR3 (Nicholas et al., 2008). Thus, excessive IP-10 and its signaling to CXCR3 on activated B cells might favor persistence of autoreactive PCs, suggesting that targeting JEM Vol. "
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    • "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 (Nicholas, 2008). CD19(hi)CD21(lo/neg) B cells of uncertain origin are expanded also in common variable immunodeficiency patients with autoimmune features (Warnatz et al, 2002). "
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