Journal
CLINICAL IMMUNOLOGY
Volume 126, Issue 2, Pages 189-201Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2007.10.004
Keywords
B lymphocytes; memory B cells; systemic lupus; erythematosus; CD19; autoimmunity; autoantibodies; Sm antigen
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Funding
- NIAID NIH HHS [R01 AI043587, R01 AI043587-10, AI29576, AI43587] Funding Source: Medline
- NIEHS NIH HHS [F30 ES014519] Funding Source: Medline
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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 phosphorytated 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 conal 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. (c) 2007 Elsevier Inc. All rights reserved.
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