The VH gene repertoire of splenic B cells and somatic hypermutation in systemic lupus erythematosus.
In systemic lupus erythematosus (SLE) it has been hypothesized that self-reactive B cells arise from virgin B cells that express low-affinity, nonpathogenic germline V genes that are cross-reactive for self and microbial antigens, which convert to high-affinity autoantibodies via somatic hypermutation. The aim of the present study was to determine whether the VH family repertoire and pattern of somatic hypermutation in germinal centre (GC) B cells deviates from normal in SLE. Rearranged immunoglobulin VH genes were cloned and sequenced from GCs of a SLE patient's spleen. From these data the GC V gene repertoire and the pattern of somatic mutation during the proliferation of B-cell clones were determined. The results highlighted a bias in VH5 gene family usage, previously unreported in SLE, and under-representation of the VH1 family, which is expressed in 20-30% of IgM+ B cells of healthy adults and confirmed a defect in negative selection. This is the first study of the splenic GC response in human SLE.
Fraser
Nicola L W
NL
Division of Immunology, Infection and Inflammation, University of Glasgow, Western Infirmary, Glasgow, Scotland, UK. nw21y@clinmed.gla.ac.uk
Rowley
Gary
G
Field
Max
M
Stott
David I
DI
D001402:B-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D003062:Codon; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D018858:Germinal Center / Q000737:chemistry / Q000166:cytology / Q000276:immunology; D006801:Humans; D007120:Immunochemistry; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012694:Serine / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin; D013154:Spleen / Q000166:cytology / Q000276:immunology*
D003062:Codon; D007135:Immunoglobulin Variable Region; D012694:Serine