preview

Allelic Exclusion Analysis

Decent Essays

According to an article by Christian Vettermann and Mark Schlissel, allelic exclusion is the driving factor behind B cell monospecificity. The authors specifically point to V(D)J recombination as the point in which allelic exclusion is established. The process of V(D)J recombination is random and imprecise, leading to a majority of resulting Ig genes that are not functional. Non functional genes are those that are unarranged, incompletely rearranged, or productively rearranged but encodes for a non pairing Ig chain (therefore cannot be put onto the surface of the cell). According to the authors, three models address allelic exclusion of immunoglobulin genes. The first is the asynchronous recombination model. In this model proposes that the slow and inefficient activation of the Ig gene chromatin limits the frequency of recombination events to one per cell. Secondly, the stochastic model argues that Ig rearrangement is maximally efficient but that the random nature of V(D)J recombination often leads to only one functional Ig allele per cell. Thirdly, the feedback inhibition model argues that gene products or intermediates inhibit Ig gene rearrangements, therefore only one allele is made. …show more content…

al. in 2004 heavily leans on the feedback inhibition model as the major contributor to allelic exclusion in B cells. They studied the effect of phospholipase Cγ1 (PLCγ1), which is expressed throughout B cell development and plays a role in pre-B-cell receptor signaling. When there is reduced expression of PLCγ1 there is impeded early B cell development at the pro-B to pre-B cell transition (Wen et. al., 2004). They also found that Ig heavy chain allelic exclusion was impaired, thus causing defective pre-BCR signaling (Wen et. al., 2004). Rearranged light chains combine with the previously rearranged heavy chain to generate surface IgMs to form the B-cell receptor. This B cell receptor changes the progenitor cell to an immature B

Get Access