Counting V, D, and J Gene Segments for the Different TCR and BCR Chains

TCR Alpha Chain:

• V segments: ~50-100 TRAV gene segments
• No D segments
• J segments: ~60 TRAJ gene segments

TCR Beta Chain:

• V segments: ~50-100 TRBV gene segments
• D segments: 2 TRBD gene segments
• J segments: ~10-15 TRBJ gene segments

TCR Gamma Chain:

• V segments: ~5-10 TRGV gene segments
• No D segments
• J segments: ~5 TRGJ gene segments

TCR Delta Chain:

• V segments: ~8 TRDV gene segments
• D segments: 3 TRDD gene segments
• J segments: ~4 TRDJ gene segments

BCR Heavy Chain:

• V segments: ~50 IGHV gene segments
• D segments: ~25 IGHD gene segments
• J segments: ~6 IGHJ gene segments

BCR Lambda Light Chain:

• V segments: ~30 IGLV gene segments
• No D segments
• J segments: ~4-5 IGLJ gene segments

BCR Kappa Light Chain:

• V segments: ~40 IGKV gene segments
• No D segments
• J segments: ~5 IGKJ gene segments

During lymphocyte development, one V, (D), and J gene segment from each set is randomly rearranged to encode the variable domain for the respective TCR or BCR chain via V(D)J recombination.

Diversity from V, D, and J segment mixing and matching

The number of each type of gene segment contributes to the huge diversity potential of TCRs and BCRs. For example, for the TCRβ chain there are ~50-100 x 2 x 10-15 = ~1000-3000 possible VDJ combinations before accounting for junctional diversity.

This genomic makeup allows lymphocytes to generate millions to billions of unique antigen receptor specificities to recognize a vast array of antigens.

Comparing V, D, and J Gene Segments Counts for Humans and Mice

There are significant differences in the number of V, D, and J gene segments for B cell receptor (BCR) and T cell receptor (TCR) loci between humans and mice.

BCR Heavy Chain:
Humans – ~50 VH, ~25 DH, ~6 JH
Mice – ~100-200 VH, ~10-12 DH, ~4 JH

BCR Kappa Light Chain:
Humans – ~40 VK, ~5 JK
Mice – ~100-200 VK, ~5 JK

BCR Lambda Light Chain:
Humans – ~30 VL, ~4-5 JL
Mice – ~3 VL, ~1 JL

TCR Alpha Chain:
Humans – ~50-100 TRAV, ~60 TRAJ
Mice – ~100 TRAV, ~60 TRAJ

TCR Beta Chain:
Humans – ~50-100 TRBV, 2 TRBD, ~10-15 TRBJ
Mice – ~20 TRBV, 2 TRBD, ~12-13 TRBJ

TCR Gamma Chain:
Humans – ~5-10 TRGV, ~5 TRGJ
Mice – ~7 TRGV, ~4 TRGJ

TCR Delta Chain:
Humans – ~8 TRDV, 3 TRDD, ~4 TRDJ
Mice – ~10+ TRDV, 2 TRDD, 2 TRDJ

In general, mice have an expanded repertoire of V gene segments compared to humans, especially for BCRs. This increased diversity may help compensate for mice having fewer D and J gene segments in some loci.

The differences likely reflect evolutionary divergence as well as distinct immune challenges faced by each species. Regardless, both species can generate highly diverse BCR and TCR repertoires through V(D)J recombination of these gene segments.

Next Topic: “GOD” Mode: Generation of Diversity in BCRs and TCRs

Source: Claude 3 Sonnet response prompted and edited by Joel Graff.

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