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

Clin Immunol. 2008 Feb;126(2):189-201. doi: 10.1016/j.clim.2007.10.004.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19 / blood*
  • Antigens, CD19 / immunology
  • Autoantigens / blood
  • Autoantigens / immunology
  • Autoimmunity
  • B-Lymphocyte Subsets / immunology*
  • Chemokine CXCL9 / blood
  • Chemokine CXCL9 / immunology
  • Female
  • Humans
  • Immunologic Factors / therapeutic use
  • Immunologic Memory*
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / physiopathology
  • Male
  • Middle Aged
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Receptors, CXCR3 / blood
  • Receptors, CXCR3 / immunology
  • Ribonucleoproteins, Small Nuclear / blood
  • Ribonucleoproteins, Small Nuclear / immunology
  • Rituximab
  • snRNP Core Proteins

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD19
  • Autoantigens
  • CXCL9 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL9
  • Immunologic Factors
  • Receptors, CXCR3
  • Ribonucleoproteins, Small Nuclear
  • snRNP Core Proteins
  • Rituximab