Insights into the regulation of immunoglobulin light chain gene rearrangements via analysis of the kappa light chain locus in lambda myeloma.
Immunology
; 112(3): 420-7, 2004 Jul.
Article
en En
| MEDLINE
| ID: mdl-15196210
Accumulating evidence indicates that B cells may undergo sequential rearrangements at the light chain loci, despite already expressing light chain receptors. This phenomenon may occur in the bone marrow and, perhaps, in germinal centers. As immunoglobulin (Ig)kappa light chains usually rearrange before Iglambda light chains, we analysed, by polymerase chain reaction, the Igkappa locus of bone marrow mononuclear cells from 29 patients with Iglambda myeloma to identify earlier recombinations in marrow plasma cells. The results demonstrated that Igkappa alleles were inactivated via the kappa-deleting element, presumably prior to V(kappa)-J(kappa) rearrangement, in many cases. Eighteen alleles (16 myeloma clones, 55%) showed V(kappa)-J(kappa) rearrangements, with increased utilization of 5' distant V(kappa) and 3' distant Jkappa gene segments (Jkappa4, 56%), an indication of multiple sequential rearrangements. In-frame, potentially functional V(kappa)-J(kappa) rearrangements were found in approximately one-third of available rearrangements (as expected by chance), each one in different myeloma clones: three were germline encoded, while one had several nucleotide substitutions, suggesting inactivation after the onset of somatic hypermutation. Three of four potentially functional V(kappa)-J(kappa)rearrangements involved V(kappa)4-1, a segment considered to be associated with autoimmunity. These findings provide insights into the regulation of light chain rearrangements and support the view that B cells may occasionally undergo sequential light chain rearrangements after the onset of somatic hypermutation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Linfocitos B
/
Reordenamiento Génico de Cadena Ligera de Linfocito B
/
Mieloma Múltiple
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Immunology
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Reino Unido