Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus

J Immunol. 2000 Nov 15;165(10):5970-9. doi: 10.4049/jimmunol.165.10.5970.

Abstract

In patients with active systemic lupus erythematosus (SLE), a marked B lymphocytopenia was identified that affected CD19(+)/CD27(-) naive B cells more than CD19(+)/CD27(+) memory B cells, leading to a relative predominance of CD27-expressing peripheral B cells. CD27(high)/CD38(+)/CD19(dim)/surface Ig(low)/CD20(-)/CD138(+) plasma cells were found at high frequencies in active but not inactive SLE patients. Upon immunosuppressive therapy, CD27(high) plasma cells and naive 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 V(H)3 family members with multiple somatic mutations. CD27(high) plasma cells showed a similar degree of somatic hypermutation, but preferentially employed V(H)4 family members. These results indicate that there are profound abnormalities in the various B cell compartments in SLE that respond differently to immunosuppressive therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Adolescent
  • Adult
  • Aged
  • Antigens, CD*
  • Antigens, CD19 / biosynthesis
  • Antigens, Differentiation / biosynthesis
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / pathology*
  • Base Sequence
  • Female
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • HLA-DR Antigens / biosynthesis
  • Homeostasis / immunology*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulins / biosynthesis
  • Immunologic Memory
  • Immunophenotyping
  • Immunosuppressive Agents / therapeutic use
  • Interphase / immunology
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / genetics
  • Lupus Erythematosus, Systemic / pathology*
  • Lymphocyte Count
  • Lymphopenia / blood
  • Lymphopenia / chemically induced
  • Lymphopenia / immunology
  • Lymphopenia / pathology
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Middle Aged
  • Molecular Sequence Data
  • Mutation
  • NAD+ Nucleosidase / biosynthesis
  • Proteoglycans / biosynthesis
  • Syndecan-1
  • Syndecans
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / blood
  • fas Receptor / biosynthesis

Substances

  • Antigens, CD
  • Antigens, CD19
  • Antigens, Differentiation
  • HLA-DR Antigens
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulins
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • Proteoglycans
  • SDC1 protein, human
  • Syndecan-1
  • Syndecans
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • fas Receptor
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • NAD+ Nucleosidase
  • ADP-ribosyl Cyclase 1