7.1 VDJ Recombination and B-Cell Receptor Genes

B cells like other APCs express both MHC I & II

Both Mice & human

• Light & heavy chain are on different chromosomes

• The light chain is on two different chromosomes

• The heavy chain is on one chromosome

BCR

• Is an antibody & an antibody is symmetrical

BCR have 2 heavy & 2 light chains

• Both heavy chain transcripts are the same

• Both light chain transcripts are the same

How are TCR & BCR similar?

• you only need to undergo VDJ recombination for 1 version of the heavy chain & 1 version of the light chain

• Heavy chain rearrangement: D & J recombine first then V joins the already recombined DJ

• Same proteins used for VDJ recombination (rag ½ etc)

Variable domain of each chain is where the V(D)J segments are found

Review of Proteins Necessary for V(D)J Recombination

RSS in BCR Genes Uses the Same Heptamer/Nonamer, 12-23 Rules

• The nonamer & heptamer order is reversed for the 12 RSS & 23 RSS

• This may help you remember the order of RSS for the 23

  • 7239 the 7 stands for heptamer

• Online definition

  • A 23 base pair (bp) spacer is a specific DNA sequence, 23 nucleotides long, located between conserved heptamer and nonamer sequences in recombination signal sequences (RSSs) that flank V, D, and J gene segments

  • Each RSS contains a conserved heptamer (7 base pair sequence) and a nonamer (9 base pair sequence). 

How many BCR light chains versions are there?

What are they called?

• There are 2 BCR light chain versions

• They are called:

  • Kappa (k)

  • Lambda (λ)

BCR Kappa light chain (k)

• The RSS in BCR Kappa light chain is similar to TCR light chain where the 12 RSS is downstream of V and the 23 RSS is upstream of J

BCR Lambda light chain (λ)

BCR heavy chain

• Remember a 12 RSS aligns with a 23 RSS so it makes sense that the 23 RSS would be adjacent to V & J

How do BCR & TCR differ?

• A BCR’s heavy & light chain have constant domains

• TCRs don’t have constant domains, they have a membrane bound piece. This membrane bound piece doesn’t vary. In B-cells you can pick a different version of the constant region, which will allow it to have different functions (antibody isotypes).

B-cell development Stages

• Heavy chain is rearranged first because..

• The pro …

• The pre..