Organization of human immunoglobulin heavy chain diversity gene loci.

Abstract

The variable region of immunoglobulin heavy chain is encoded by three separate genes on the germline genome: variable (VH), diversity (DH) and joining (JH) genes. Most human DH genes are encoded in 9‐kb repeating sequences. We determined the nucleotide sequence of a 15‐kb DNA fragment containing more than one and a half of these repeating units, and identified 12 different DH genes. Based on the sequence similarities of DH coding and the surrounding regions, they can be classified into six different DH gene families (DXP, DA, DK, DN, DM and DLR). Nucleotide sequences of DH genes belonging to different families diverge greatly, while those belonging to the same families are well conserved. Since the 9‐kb DNA containing the six DH genes are multiplied at least five times, the total number of DH genes must be approximately 30. These DH genes are sandwiched by 12‐nucleotide spacer signals. Most of the somatic DH sequences found in the published VH‐DH‐JH structures (the somatic DH segment being defined as the region which is not encoded either by germline VH or JH gene) were assigned to one of the germline DH genes. Other than these typical DH genes, however, we found a new kind of DH gene (which we termed DIR) the spacer lengths of whose neighbouring signals were irregular. The DIR gene appears to be involved in DIR‐DH or DH‐DIR joining by inversion or deletion. Two of the somatic DH sequences were assigned to the DIR genes. Long N segments might, therefore, originate from DIR genes.

Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 Concerted Action BMH4-CT98-3936

“…50 Based on sequence homology, the 27 DH segments can be grouped into seven families: DH1 (formerly known as DM), DH2 (DLR), DH3 (DXP), DH4 (DA), DH5 (DK), DH6 (DN), and DH7 (DQ52); all families comprise at least four members, except for the seventh that consists of the single DH7-27 segment just upstream of the JH region ( Figure 4a). 50,51 Recombination between any of the DH and JH segments will result in the formation of incomplete DH-JH joints, which can easily be detected in BM-derived CD10 þ /CD19 À precursor B cells, 52,53 and hence also in a subset (20-25%) of precursor Bcell ALLs, which show an immature genotype. 54 Sequencing revealed a predominance of DH2 (DH2-2), DH3 (DH3-9), and DH7-27 gene segments in precursor B-ALL, comprising 36, 33, and 19% of all identified segments, respectively.…”

Improved assessment of minimal residual disease in B cell malignancies using fluorogenic consensus probes for real-time quantitative PCR

“…20 J H elements and individual D H segments were identified by comparison with published germline sequences. [21][22][23][24][25][26] …”

Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment.

“…Using the binomial probability model, we calculated that the distribution of six replacement mutations in CDR of a (corrected) total of 13 mutations had a low probability of occurring at random (P = 0.046). Positive selection of replacement mutations in CDR has been observed in murine immune responses and presumably reflects selection for enhanced antigen binding (31 (32) and homology of the Sp2 D segment ( 17 nucleotides) with Dxp4 (33) (Figs. 2 and 4).…”