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THU0057 Disturbed peripheral b cell homeostais in sle
  1. T Dörner1,
  2. M Odendahl2,
  3. A Jacobi1,
  4. A Hansen1,
  5. F Hiepe1,
  6. GR Burmester1,
  7. PE Lipsky3,
  8. A Radbruch2
  1. 1Department Medicine, Charite, Berlin, Germany
  2. 2Deutsches Rheumaforschungszentrum, Charite, Berlin, Germany
  3. 3NIAMS, NIH, Bethesda, MD, USA

Abstract

Background The distribution of peripheral B cell subpopulations in SLE is unknown, although a variety of humoral abnormalities are known.

Objectives The phenotype and Ig heavy chain gene usage of peripheral B cell subpopulations of patients with active systemic lupus erythematosus (SLE) were examined.

Methods Peripheral B cells were characterised by FACS analysis and B cell subpopulations of one patient were characterised for V(D) J gene rearrangements.

Results In patients with SLE, there was a marked B lymphocytopenia that affected CD19+/CD27- naïve B cells more than CD19+/CD27+ memory B cells leading to a relative predominance of CD27 expressing peripheral B cells. In contrast, CD27high/CD38+/CD19dim/surface Iglow/CD20-/syndecan-1+plasma cells were found at an enhanced frequency in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27high plasma cells and naïve CD27- B cells were markedly decreased in the peripheral blood. Mutational analysis of V gene rearrangements of individual B cells confirmed that CD27+ B cells coexpressing IgD were memory B cells preferentially using VH3 family members with multiple somatic mutations. CD27high plasma cells showed a similar degree of somatic hypermutation, but preferentially employed VH4 family members.

Conclusion These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.

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