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

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 antiSm 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.

Altered expression of signalling lymphocyte activation molecule (SLAM) family receptors CS1 (CD319) and 2B4 (CD244) in patients with systemic lupus erythematosus

“…According to a recent study, the majority of CD19 + B cells are IgD + and CD27 -, indicating naive B cells [52]. They also reported CD19-high B cells as autoreactive memory B cells, and the frequency of this population correlates with disease activity [52,53]. Also, active SLE disease has been shown to correlate with a high frequency of plasma cells, which express high levels of CD27 and low levels of CD19 [54,55].…”

Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus

“…Until now, analysis of B cell subsets in the peripheral blood of SLE patients has revealed a number of abnormalities (7), such as an increased frequency of transitional type 1 (T1) B cells and pre-naive B cells (8,9), CD27 high or HLAϪ DR high CD27 high plasmablasts (10,11), CD19 high B cells (12,13), and CD21 low/Ϫ B cells (14,15). In general, CD27 is a reliable surface marker for human memory B cell identification (16).…”

Acceleration of diabetes development in CXC chemokine receptor 3 (CXCR3)-deficient NOD mice

“…Although this receptor is also expressed on Cd8 + T cells, B cells, macrophages, dendritic cells, natural killer (NK) cells and regulatory T cells (Tregs), it is expressed mainly on Th1 cells and can lead them to sites of tissue inflammation in response to CXCR3-binding chemokines, such as CXCL9/monokine induced by IFN-γ (Mig), CXCL10/IP-10 and CXCL11/ IFN-inducible T cell α chemoattractant (I-TAC) [6][7][8][9][10][11]. Therefore, it is reasonable to assume that there is an amplification loop for Th1 immune responses between Th1 cells, which produce IFN-γ, and pancreatic beta cells, which produce CXCL10, in response to this cytokine, thereby attracting more Cxcr3-expressing Th1 cells to the affected site and amplifying the ongoing Th1 response.…”