title: Unusual sequence of immunoglobulin L-chain rearrangements in a gamma heavy chain disease patient.
abstract: Patients with gamma heavy chain disease (gamma-HCD) generally produce incomplete immunoglobulin (Ig) gamma-heavy chains (gamma-HCD protein) which cannot associate with light chains (IgL). In most patients Bence Jones proteins (BJP) are not observed. However, in the 61-year-old patient WIN we found gamma l-HCD proteins and lambda BJP in serum and urine. WIN gamma l-HCD protein does not carry the Ig Fd region, has a molecular weight of 33.5 kDa, and the seven N-terminal amino acid residues are not translated from any of the known immunoglobulin heavy chain (IgH) gene sequences. These residues are followed by the C gamma l-hinge region. In DNA from peripheral blood lymphocytes of patient WIN we found bands representing dominant rearrangements in one of the two alleles of the IgH, Ig kappa and Ig lambda locus. Taken together, the data from protein and DNA analysis strongly suggest, albeit do not formally prove, that one dominant B-cell clone which carries a rearranged and a non-rearranged allele of each Ig locus produces gamma-HCD protein and lambda BJP. The productive lambda-gene rearrangement in this clone thus has not been preceded by abortive rearrangements in both kappa-locus alleles. Lymphocytes with an unusual sequence of IgL-chain gene activation seem to be involved in the case of gamma-HCD described here.
authors.affiliation: Medizinische Universitätsklinik, Freiburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hauke
authors.forename: E
authors.initials: E
authors.lastname: Schiltz
authors.forename: K J
authors.initials: KJ
authors.lastname: Bross
authors.forename: A
authors.initials: A
authors.lastname: Hollmann
authors.forename: H H
authors.initials: HH
authors.lastname: Peter
authors.forename: U
authors.initials: U
authors.lastname: Krawinkel
mesh_terms: D000595:Amino Acid Sequence; D015139:Blotting, Southern; D002850:Chromatography, Gel; D002874:Chromosome Mapping; D004247:DNA / Q000032:analysis; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006362:Heavy Chain Disease / Q000276:immunology*; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D007142:Immunoglobulin gamma-Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007142:Immunoglobulin gamma-Chains; C032598:heavy chain disease proteins, human; D004247:DNA