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Secondary V(D)J recombination in B-1 cells
1Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA.
Nature
|February 9, 1999
Summary
B-1 B cells may produce autoreactive antibodies due to secondary V(D)J recombination of immunoglobulin genes, a process involving recombinase-activating genes (RAG1 and RAG2). This occurs outside organized lymphoid organs, particularly in autoimmune-prone mice.
Area of Science:
- Immunology
- Molecular Biology
- Autoimmunity
Background:
- B-1 B cells are prone to auto-antibody production.
- Signaling pathways controlling B-1 cell growth are known, but the cause of autoreactivity is unclear.
Purpose of the Study:
- To investigate the molecular mechanisms underlying the autoreactive antibody production by B-1 B cells.
- To explore the role of immunoglobulin gene recombination in B-1 cell autoreactivity.
Main Methods:
- Analysis of recombinase-activating gene (RAG1 and RAG2) expression in B-1 cells.
- Investigation of secondary V(D)J recombination of immunoglobulin genes in B-1 cells.
- Assessment of RAG messenger RNA and recombination levels in B cells from NZB mice.
Main Results:
- B-1 B cells express RAG1 and RAG2, enabling secondary V(D)J recombination of immunoglobulin genes.
- B cells from autoimmune-prone NZB mice exhibit elevated RAG messenger RNA and recombination levels.
- Evidence suggests secondary immunoglobulin gene rearrangements occur outside organized lymphoid tissues.
Conclusions:
- Secondary immunoglobulin gene rearrangements in B-1 B cells may contribute to autoreactive antibody development.
- RAG-mediated recombination outside lymphoid organs could be a mechanism driving autoimmunity.
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