Disturbed peripheral B lymphocyte homeostasis in systemic lupus erythematosus.
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.
Odendahl
M
M
Deutsches Rheuma-Forschungszentrum Berlin, Charite University Hospital, Berlin, Germany.
Jacobi
A
A
Hansen
A
A
Feist
E
E
Hiepe
F
F
Burmester
G R
GR
Lipsky
P E
PE
Radbruch
A
A
Dörner
T
T
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D018941:Antigens, CD19 / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006706:Homeostasis / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis; D007156:Immunologic Memory; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007399:Interphase / Q000276:immunology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009244:NAD+ Nucleosidase / Q000096:biosynthesis; D011509:Proteoglycans / Q000096:biosynthesis; D053668:Syndecan-1; D053667:Syndecans; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000097:blood; D019014:fas Receptor / Q000096:biosynthesis
D015703:Antigens, CD; D018941:Antigens, CD19; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1