Dominance of hydrophobic reading frames in complementarity determining region 3 of variable heavy chain genes from a patient with untreated SLE
© BioMed Central Ltd 2001
Received: 15 January 2001
Published: 26 January 2001
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of multiple autoantibodies (AAb), especially anti-dsDNA Ab. It is not known whether an aberrant V(D)J recombination process itself predisposes to the generation of autoreactive Ab, or whether abnormalities in selection influences can lead to the generation of AAb. Immunoglobulin (Ig) heavy (H) and Ig light chains of an antibody are generated from variable (V), diversity (D) and joining (J) gene segments through V(D)J rearrangements. Diversification mechanisms inherent to the rearrangement reaction ensure that D elements can potentially be used in all reading frames (RF). In addition, D and J elements of the IgH chains encode the complementarity determining region (CDR) 3 that constitutes a significant part of the Ig antigen binding site. Since it has been suggested that the CDR3 of Ab in SLE is different from that found in normals, we compared the CDR3 obtained from Ab of an untreated SLE patient with that from normal individuals. D segments of Ab from normal donors are preferentially used in RF II (26/48, p* 0.001) that most often encodes hydrophilic antibodies. Comparison of productive and nonproductive rearrangements suggests, that this is the result of the recombinational process rather than selection. In contrast, RF II was significantly less often used in SLE Ab (4/17, p* 0.03). In both, normal and SLE Ab, D segments were significantly less often found utilizing RF that encode stop codons. Similar to the usage of RF II, in normals this seems to be the result of the recombination process rather than selection. Because of the low number of nonproductive rearrangements in the SLE analysis it is not possible to estimate whether this results from selection or the recombination process. In contrast to the analysis of the RF, no significant difference between the length or composition of the CDR3 from SLE and normal Ab was found.