Immunology for Non-Immunologists: B and T Cell Receptors

Our new series, Immunology for Non-Immunologists, will focus on key concepts to help scientists and researchers without extensive immunology backgrounds understand the functions and use cases for our immune cell products.

Our first post in this series focuses on the structure and function of B cell and T cell receptors. If you have other questions about using our products in your lab, just ask one of our scientists! No question is too big or too small; we’re here to help!

B Cell and T Cell Receptors: Not Your Garden-Variety Receptors

Receptors and Ligands

All cells are equipped with receptors, either intracellular or on the cell surface, that bind with outside ligands to transmit signals or initiate cell changes.

Typical cell receptors will only bind with a specific ligand or family of ligands. For example, the insulin receptor will bind insulin, not estrogen. That is not the case for B cell receptors (BCRs) or T cell receptors (TCRs).

Image Source: Khan Academy

Genetic Rearrangement

BCRs and TCRs are both created by genetic rearrangements within the B cell or T cell. There are three or four different gene segments that make up each receptor in B cells and T cells, depending on the chain type:

  1. Variable “V” Gene
  2. Joining “J” Gene
  3. Constant “C” Gene
  4. Diversity “D” Gene (in beta chain of TCRs and heavy chain of BCRs)

Think of the assembly of a BCR or TCR as a Las Vegas-sized buffet: You select an entree, side dish, and dessert from an endless lineup of options to fill your plate. VJ or V(D)J recombination joins these gene segments together to form a complete protein chain within B cells and T cells.

Unique Combinations

With hundreds of V, J, C, and D genes, there are an astounding 1012 possible arrangements for BCRs and TCRs!

In addition to the combination of gene segments, there is even more diversity generated by the pairing of the heavy and light chains of the BCR and the alpha-beta chains of the TCR. And if that weren’t enough, there are nucleotides added or removed to create unique joins between the gene segments.

All of these possibilities lead to lymphocytes that express unique BCRs or TCRs, which means that each B cell and T cell will only bind with certain ligands. For any given pathogen, only a subset of B cells and T cells will respond.

T Cell Receptor Diversity
T-cell receptor gene rearrangement. (a) Variable (V), joining (J) and constant regions (C) constitute the TCR α-chain. (b) Variable (V), joining (J) and constant regions (C) constitute the TCR β-chain, with an additional diversity (D) region. Segments from each region are recombined, with additional nucleotide additions, to generate each rearranged TCR. These processes generate substantial T cell diversity. (c,d) Hypervariable complementarity-determining regions (CDR1-CDR3) of the α-chain (c) and β-chain (d). CDR1 and CDR2 regions are encoded on the V region, while the most variable CDR3 region straddles the V(D)J junction.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528489/#RSTB20140291C3
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