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Biases in Ig lambda light chain rearrangements in human intestinal plasma cells
Wen Su1, Laurent Boursier, Archana Padala
1Department of Histopathology, GKT Medical School, St Thomas' Campus, London, United Kingdom.
Journal of Immunology (Baltimore, Md. : 1950)
|February 7, 2004
Summary
Human intestinal plasma cells show unique immunoglobulin lambda gene rearrangements. Specific patterns in out-of-frame rearrangements suggest secondary recombination events are crucial for immune cell development.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Human intestinal plasma cells originate from germinal centers in gut-associated lymphoid tissues.
- Understanding B cell repertoire development is key to immune system function.
Purpose of the Study:
- To compare immunoglobulin lambda (IgVlambdaJlambda) rearrangements in human colonic plasma cells and Peyer's patch B cells.
- To investigate the role of Vlambda gene usage and rearrangement patterns in intestinal plasma cells.
Main Methods:
- Microdissection of human colonic lamina propria plasma cells and Peyer's patch B cell subsets.
- Immunohistochemical staining and PCR-based sequence analysis of IgVlambdaJlambda rearrangements.
- Comparison of in-frame and out-of-frame rearrangements between cell populations.
Main Results:
- In-frame IgVlambdaJlambda rearrangements in plasma cells mirror those in mantle cells, indicating broad Vlambda segment usage.
- Out-of-frame rearrangements involving Vlambda1 and Vlambda2 are rare in plasma cells, while Vlambda5 rearrangements increase.
- Biased in-frame:out-of-frame ratios observed in specific Vlambda families.
- Out-of-frame rearrangements in plasma cells often avoid Jlambda1, suggesting secondary recombination.
Conclusions:
- Antigenic selection does not strongly bias Vlambda segment usage in intestinal plasma cells.
- Secondary recombination events likely modify IgVlambdaJlambda rearrangements in plasma cells.
- This modification may prevent translocations during somatic hypermutation, ensuring immune system stability.