Not Germline: V(D)J Recombination in T-Cell and B-Cell Receptors

Germline refers to the genetic material inherited from parents and present in the zygote. Innate immune receptors, like Toll-like receptors (TLRs) and NOD-like receptors (NLRs), are encoded by single germline genes that are passed on unchanged from parents to offspring.

However, TCRs and BCRs are not directly encoded by germline genes. Instead, their genes exist in several different gene segments scattered across the genome – Variable (V), Diversity (D), and Joining (J) gene segments for BCRs, and just V and J segments for TCRs.

During T and B cell development, the V(D)J recombination process randomly rearranges one V, (D), and J gene segment from the set of germline segments to create a unique rearranged V(D)J sequence that encodes the variable region of the TCR or BCR. This recombination introduces tremendous diversity into the TCR and BCR repertoire that is not present at the germline level.

So in summary, while innate receptors are directly encoded by inherited germline genes, the TCR and BCR genes undergo programmed rearrangement and are therefore not considered germline receptors, even though the gene segments they rearrange originate from the germline. V(D)J recombination allows immense diversity of these antigen receptors that could not be achieved from germline sequences alone.

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

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

• Immunology (Table of Contents for Entire Course – FREE!)
  • Other Content for Unit 4: Development of T Cells and B Cells