PMID: 9440145Jan 1, 1997Paper

Analysis of VH gene rearrangements from synovial B cells of patients with rheumatoid arthritis reveals infiltration of the synovial membrane by memory B cells

Rheumatology International
A GauseM Pfreundschuh

Abstract

The VH gene (Variable gene segments of the heavy chain locus) repertoire can be investigated by DNA analysis of rearranged immunoglobulin VH genes, which also allows for an indirect estimation of antibody selection by analysis of somatic mutations. Using a polymerase chain reaction (PCR) it is also possible to analyse these genes in small numbers of cells or even single cells. This approach was chosen to investigate germinal centre like lymphocyte follicles in the synovial membranes of two patients with rheumatoid arthritis (RA) in order to analyse the local humoral immune response in RA. Individual B-cell aggregates of synovial membrane of two patients with RA were isolated by micromanipulation from microscopic slides. VH-DH-JH (variable, diversity, and joining segments of the heavy chain locus) rearrangements in all possible VH-JH combinations were amplified from these B cell foci, cloned and subjected to sequence analysis. Sequence analysis revealed that most of the rearranged VH genes were somatically mutated with at least 1% (range 1.3-14.9%) somatic mutations and therefore were derived from antigen-selected memory B cells. Intraclonal diversity in one-third of the clones indicated the generation of memory B cells in the s...Continue Reading

Citations

Jul 5, 2001·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·A Gause, C Berek
Jun 1, 2007·Autoimmunity Reviews·Angela Lee ForemanM Eric Gershwin
Feb 1, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rebecca A SweetMark J Shlomchik
Sep 28, 2018·Frontiers in Immunology·Elena PipiFrancesca Barone

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