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Gene conversion as a part of BCR diversification

A new paper shows that gene conversion from a different chromosome is another means of antibody diversification.

This could either happen through RAG or through double-stranded breaks made by AID at a later stage of development.

Here’s the paper:

Here’s a commentary:

Apparently AID-mediated gene conversion is observed in chickens and fish, as reviewed in this paper:

[As if repertoire analysis wasn’t complex enough already… sigh.]

I remember that I occasionally encountered joints of V segments to genomic regions on other chromosomes when doing manually sequence analysis. However, there never seemed to be a consistent target, which was very likely caused by absence of selective pressure in the experimental setup.
In addition, I now realized that IgBLAST (at least versions 1.3.0 and 1.4.0) has a hard-coded maximum number of base pairs (bp) that it will accept in between V_end and J_start. The limit is set to 90 bp, everything above will remove the identified J segments from the hit list. There is also a limit for the distance between V_end and D_start, however it seems to be different between the stand-alone version (40 bp) and the online tool (55 bp).
For our processing pipeline, sequences without any identified J segments will be excluded from subsequent analysis, thus we would effectively filter out events with long CDR3s as described in this paper. Anyone encountered similar issues?

Our pipeline also typically excludes reads with good V but no J -which is what these antibodies would look like in NGS, unless you used PacBio. Could be interesting to go back to old datasets and look…

In chickens and rabbits, gene conversion seems to be the primary manner in which initial BCR diversity is generated. In both these species, the IGHV locus contains only a single functional V gene and many pseudogenes. Gene conversion between the functional and pseudogenes (post VDJ rearrangement), then produces receptor diversity. The following is a nice review article about V genes in chickens and rabbits: