Analysis of immunoglobulin light chain rearrangements in the salivary gland and blood of a patient with Sjögren's syndrome.
Patients with Sjögren's syndrome (SS) have characteristic lymphocytic infiltrates of the salivary glands. To determine whether the B cells accumulating in the salivary glands of SS patients represent a distinct population and to delineate their potential immunopathologic impact, individual B cells obtained from the parotid gland and from the peripheral blood were analyzed for immunoglobulin light chain gene rearrangements by PCR amplification of genomic DNA. The productive immunoglobulin light chain repertoire in the parotid gland of the SS patient was found to be restricted, showing a preferential usage of particular variable lambda chain genes (V lambda 2E) and variable kappa chain genes (V kappa A27). Moreover, clonally related V(L) chain rearrangements were identified; namely, V kappa A27-J kappa 5 and V kappa A19-J kappa 2 in the parotid gland, and V lambda 1C-J lambda 3 in the parotid gland and the peripheral blood. V kappa and V lambda rearrangements from the parotid gland exhibited a significantly elevated mutational frequency compared with those from the peripheral blood (P < 0.001). Mutational analysis revealed a pattern of somatic hypermutation similar to that found in normal donors, and a comparable impact of selection of mutated rearrangements in both the peripheral blood and the parotid gland. These data indicate that there is biased usage of V(L) chain genes caused by selection and clonal expansion of B cells expressing particular V(L) genes. In addition, the data document an accumulation of B cells bearing mutated V(L) gene rearrangements within the parotid gland of the SS patient. These results suggest a role of antigen-activated and selected B cells in the local autoimmune process in SS.
Jacobi
Annett M
AM
Department of Internal Medicine/Rheumatology and Clinical Immunology, Charite University Hospital, Berlin, Germany.
Hansen
Arne
A
Kaufmann
Olaf
O
Pruss
Axel
A
Burmester
Gerd R
GR
Lipsky
Peter E
PE
Dörner
Thomas
T
D000368:Aged; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D008969:Molecular Sequence Data; D010306:Parotid Gland / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology*
D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains