Question

In B cells, how many chances are there to make a productive heavy chain and how many chances are there to make a productive light chain? The options are 2 chances for light & 2 chances for heavy OR 2 chances for heavy & 4 chances for light. Please explain why

Answer 1

There are 2 chances to make a productive heavy chain

Heavy chain production occurs in the pro-B cells. Every B cell has 2 copies of the heavy chain locus on each homologous chromosome derived from the father and mother respectively. During development, gene rearrangements can occur on both the chromosomes. Therefore, if the rearrangement on one chromosome becomes non-productive, it can still form a productive rearrangement on the other homologous chromosome.

If the gene rearrangement in both the homologous chromosomes fail to produce a productive rearrangement, then the cell does not develop further as it loses its potential to form the heavy chain of the immunoglobulin.

The first recombination occurs between D and J segments during which all other genes in between are deleted. The second recombination occurs between the newly formed DJ segment and the V segment present upstream, deleting all the genes in between during the process. This happens as the heavy chain genes are found within a single gene locus (IGH) and in the same orientation as the constant regions. Thus, if the new VDJ complex forms non-productive product, then a new combination cannot be formed as all genes have been deleted.

There are multiple chances to make a productive light chain

Light chain production occurs in the pre-B cells.

light chain genes in humans are found as two separate gene loci-the κ locus and the λ locus. Many of the genes in the k locus has opposite orientation as that of the constant region genes. This helps to retain the gene segments between V and J in case of a non-productive chain formation. Thus, the all the V and J genes remain available for secondary rearrangements until a productive VJ combination occurs