V(D)J Rearrangement Is Dispensable for Producing CDR-H3 Sequence Diversity in a Gene Converting Species

The origin of CDR H3 structural diversity.

Antibody complementarity determining region (CDR) H3 loops are critical for adaptive immunological functions. Although the other five CDR loops adopt predictable canonical structures, H3 conformations have proven unclassifiable, other than an unusual C-terminal "kink" present in most antibodies. To determine why the majority of H3 loops are kinked and to learn whether non-antibody proteins have...

CDR-H3 diversity is not required for antigen recognition by synthetic antibodies.

A synthetic phage-displayed antibody repertoire was constructed with equivalent chemical diversity in the third complementarity-determining regions of the heavy (CDR-H3) and light (CDR-L3) chains, which contrasts with natural antibodies in which CDR-H3 is much more diverse than CDR-L3 due to the genetic mechanisms that generate antibody encoding genes. Surprisingly, the synthetic repertoire yie...

Unusual sequence of VDJ rearrangement revealed by molecular analysis in a patient with indolent lymphoma.

We report a unique case of indolent lymphoma with an unusual VDJ rearrangement. Polymerase chain reaction (PCR) analysis of bone marrow at the time of diagnosis was positive for both BCL-2/JH and CDRIII rearrangements. After treatment, the patient achieved complete remission (CR) with slow disappearance of both rearrangements (CDRIII and then BCL-2/JH). Subsequently, two new CDRIII rearrangemen...

High-Throughput Sequencing of the Expressed Torafugu (Takifugu rubripes) Antibody Sequences Distinguishes IgM and IgT Repertoires and Reveals Evidence of Convergent Evolution

B-cell antigen receptor (BCR) or antibody diversity arises from somatic recombination of immunoglobulin (Ig) gene segments and is concentrated within the Ig heavy (H) chain complementarity-determining region 3 (CDR-H3). We performed high-throughput sequencing of the expressed antibody heavy-chain repertoire from adult torafugu. We found that torafugu use between 70 and 82% of all possible V (va...

Limiting CDR-H3 Diversity Abrogates the Antibody Response to the Bacterial Polysaccharide a 1→3 Dextran