Gene conversion as a part of BCR diversification


#1

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.]


#2

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?


#3

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…


#4

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: