Evidence map›Paper›PMID 39875530›Full record

ArticleCommunications biology2025

Unveiling inverted D genes and D-D fusions in human antibody repertoires unlocks novel antibody diversity.

Ponraj Prabakaran, Abhinav Gupta, Sambasiva P Rao, Deepak Rajpal, Maria Wendt, Yu Qiu, Partha S Chowdhury

Abstract read
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ponraj PrabakaranLarge Molecules Research, Sanofi, Cambridge, MA, USA. prabakaran.ponraj@gmail.com.ORCID http://orcid.org/0000-0002-4049-4813
Abhinav GuptaLarge Molecules Research, Sanofi, Cambridge, MA, USA.
Sambasiva P RaoLarge Molecules Research, Sanofi, Cambridge, MA, USA.
Deepak RajpalTranslational Science, Sanofi, Cambridge, MA, USA.
Maria WendtLarge Molecules Research, Sanofi, Cambridge, MA, USA.
Yu QiuLarge Molecules Research, Sanofi, Cambridge, MA, USA. yu.qiu@sanofi.com.ORCID http://orcid.org/0000-0002-2078-0513
Partha S ChowdhuryLarge Molecules Research, Sanofi, Cambridge, MA, USA. pchowd15@its.jnj.com.ORCID http://orcid.org/0000-0003-0990-4658

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Antibodies, essential components of adaptive immunity, derive their remarkable diversity primarily from V(D)J gene rearrangements, particularly within the heavy chain complementarity-determining region 3 (CDR-H3) where D genes play a major role. Traditionally, D genes were thought to recombine only in the forward direction, despite having identical recombination signal sequences (12 base pair spacers) at both ends. This observation led us to question whether these symmetrical sequences might enable bidirectional recombination. We identified 25 unique inverted D genes (InvDs) in both naive and memory B cells from antibody repertoires of 13 healthy donors. These InvDs utilize all three reading frames during translation, producing distinct amino acid profiles enriched in histidine, proline, and lysine in CDR-H3s of antibodies with potential functional diversity. Notably, our analysis revealed a broader range of D-D fusions, including D-D, D-InvD, InvD-D, and InvD-InvD configurations, opening new perspectives for antibody engineering and therapeutic development.

Indexed as

Antibody DiversityComplementarity Determining RegionsV(D)J RecombinationB-LymphocytesHumansComplementarity Determining Regions

Identifiers

PMID39875530
PMCPMC11775173

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.