Biased Immunoglobulin Light Chain Gene Usage in the Shark.

Area of Science:

• Immunology
• Evolutionary Biology
• Genetics

Background:

• The nurse shark possesses a complex immunoglobulin (Ig) gene system, including multiple light chain isotypes (κ, λ, σ, σ-2) and two heavy chain isotypes (μ, ω).
• Shark Ig gene organization, characterized by minigenes with VL-JL-CL arrays, differs significantly from the mammalian system, involving independent rearrangement events.

Purpose of the Study:

• To complete the characterization of nurse shark classical Ig gene content.
• To investigate the expression patterns and usage of nurse shark kappa (κ) light chain gene clusters.
• To compare κ cluster expression with other light chain isotypes (λ, σ, σ-2) and understand the nonrandom activation of these spatially distant clusters.

Main Methods:

• Analysis of nurse shark κ gene clusters, including their minigene structure (VL-JL-CL array) and germline configuration.
• Examination of functional, nonproductive, and sterile transcripts from κ clusters.
• Investigation of κ cluster usage in young nurse sharks and comparison with other light chain isotypes.

Main Results:

• Nurse shark κ clusters are minigenes with V to J recombination over an ~500-bp interval, separated by at least 100 kb.
• Six of approximately 39 κ clusters are prerearranged in the germline (germline-joined).
• A skewed, nonrandom pattern of split gene expression was observed for κ clusters, similar for functional and nonproductive rearrangements.
• Both split and germline-joined κ genes are expressed, with germline-joined genes being more prominent in young sharks and decreasing with age.

Conclusions:

• The individual activation of spatially distant nurse shark κ clusters is a nonrandom process.
• Differential activation of multiple Ig isotypes in sharks may play a role in receptor editing.
• The distinct Ig gene organization and rearrangement mechanisms in sharks offer insights into vertebrate immune system evolution.