Clin Immunol, Vol 126, pp 189-201, 2008
A novel subset of memory B cells is enriched in autoreactivity and correlates with adverse outcomes in SLE
Nicholas MW, et al
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 CD19hi 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 CD19hi B cells have elevated CXCR3 levels and chemotax in response to its ligand CXCL9. Thus, CD19hi B cells are precursors to anti-self PCs, and identify an SLE patient subset likely to experience poor clinical outcomes.
