Hi, this is one of the fascinating issues of the adaptive immune system evolution!

The core of the 1957 clonal selection theory by Macfarlane Burnett can be simplified in the rule: one cell - one antibody. In principle, there are several mechanisms to ensure the expression of only one allele, known as allelic exclusion mechanisms. You can read nice updated reviews on that subject, for instance:

http://www.nature.com/nri/journal/v4/n10/full/nri1458.html

http://www.lsic.ucla.edu/classes/mimg/spring_05/mimgm261/witte_4_11_2.pdf

http://www.jimmunol.org/content/185/7/3801.full.pdf+html

http://www.nature.com/ni/journal/v8/n10/abs/ni1007-1015.html

https://www.researchgate.net/publication/23803312_The_origin_of_the_one_cell-one_antibody_rule

If you need a more basic information, am sure you can find it in several immunology books online.

Hope to have been of use!

Article The Origin of the “One Cell-One Antibody” Rule

Christopher, I've seen your profile and know now that you do not need a basic information! Best luck!

Thanks Rocio,

As you said, I know relatively well the basics of clonal selection with "one cell, one Ab", but what I don't quite get is if >1 allelic variant (e.g. IGHV1-2*01 and *02) can be expressed in the same individual (at large), meaning; when is the allelic variants shut down in the differentiation process of stem cell to B cell?

I guess it could also be that it's not that common with allelic variants in the genome within a single person anyway (for Ig genes), but It must occur sometimes.

The reason I'm wondering is due to the potential of finding both variants when performing deep sequencing (possibly messing up the data slightly, since I'm mainly working with nonhuman primate sequences and not with beautiful databases that exist for mice and man)

Christopher,

let me see if I understood your question.

allelic exclusion works every time a V(D)J rearrangement is ongoing, therefore, it is operative at a single cell level. Theoretically, you can have different B-cells using a single allele, let's say IGHV1-2*01, and also you can have two alleles of the same VH since stem cells have a germline IGH locus and somatic recombination can use any of the alleles in different cells. What is different every time is the VDJ CDR3 joining region. When you clone VH-DH-JH rearrangements you can have (and it occurs quite frequently) several rearrangement sequencing sharing the same VH with different CDR3 region, and even both VH alleles of the same VH and then you assume they derive from different B cells . This is ok with main stream germinal center B cells.

My work is in applied science ( human lymphoma and leukemia), so, I may have missed some basics of your original question.

And well, maybe you will have to do good to science and compile a database in order to cope with the diversity of your biological model! Anyway, IGH biology is such a fun! wish you luck with your work!