Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells

Arthritis Rheum. 2004 Jun;50(6):1918-27. doi: 10.1002/art.20274.


Objective: To determine phenotypic and functional abnormalities of blood B cell subsets in patients with systemic sclerosis (SSc).

Methods: Cell surface marker expression was determined by flow cytometry. Spontaneous apoptosis was evaluated by annexin V expression with flow cytometric analysis. IgG production by isolated IgD- memory B cells was examined by enzyme-linked immunosorbent assay.

Results: The numbers of blood CD27- naive B cells from SSc patients were increased compared with normal control cells, while memory B cells expressing medium levels of CD27 and plasmablasts expressing high levels of CD27 were reduced. In contrast, plasmablasts were the predominant population in patients with systemic lupus erythematosus (SLE). Memory B cells in SSc showed increased expression of activation markers, including CD80, CD86, and CD95, relative to normal controls. Consistent with CD95 up-regulation, SSc memory B cells exhibited augmented spontaneous apoptosis after 24-hour incubation; augmented apoptosis may explain the reduced memory B cell number. Nonetheless, isolated IgD- SSc memory B cells treated with stimuli had an enhanced ability to produce IgG. Furthermore, expression of CD19, a critical signal transduction molecule of B cells that regulates autoantibody production, was significantly increased in memory B cells as well as in naive B cells in SSc. In contrast, CD19 expression was decreased in SLE B cells.

Conclusion: SSc patients have distinct abnormalities of blood homeostasis and B cell compartments, characterized by expanded naive B cells and activated but diminished memory B cells. Our results suggest that CD19 overexpression in SSc memory B cells is related to their hyperreactivity.

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • Female
  • Homeostasis / immunology*
  • Humans
  • Hypergammaglobulinemia / immunology
  • Immunoglobulin G / metabolism
  • Immunologic Memory / immunology*
  • Lymphocyte Count
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Plasma Cells / cytology
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Scleroderma, Systemic / immunology*
  • fas Receptor / metabolism


  • Antigens, CD
  • Antigens, CD19
  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Immunoglobulin G
  • Membrane Glycoproteins
  • fas Receptor