Nicholas Matilda W, Dooley Mary Anne, Hogan Susan L, Anolik Jennifer, Looney John, Sanz Ingnacio, Clarke Stephen H
Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Clin Immunol. 2008 Feb;126(2):189-201. doi: 10.1016/j.clim.2007.10.004.
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.
我们之前报道过，一些系统性红斑狼疮（SLE）患者体内存在一群循环记忆B细胞，其CD19水平比正常水平高2倍以上。我们在此表明，CD19高表达（CD19(hi)）B细胞的存在与长期不良预后相关。这些B细胞似乎并非无反应性，因为它们表现出较高的磷酸化Syk和ERK1/2基础水平，对BCR交联有信号转导反应，并且在体外可分化为浆细胞（PC）。自身反应性抗史密斯（Sm）B细胞在这群细胞中富集，富集程度与血清抗Sm滴度的对数相关，这表明它们在分化为PC之前经历了克隆扩增。PC分化可能发生在炎症部位，因为CD19(hi) B细胞的CXCR3水平升高，并对其配体CXCL9产生趋化反应。因此，CD19(hi) B细胞是抗自身PC的前体，并确定了一个可能经历不良临床结局的SLE患者亚群。
