期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 40, 期 4, 页码 1150-1161出版社
WILEY
DOI: 10.1002/eji.200939914
关键词
GC; Ig; myasthenia gravis; Somatic hypermutation; Thymus
类别
资金
- Association Francaise Contre les Myopathies
- Dunhill Medical Trust
- Israel Science Foundation [759/01, 546/05]
- Israel Cancer Research Fund
- Human Frontiers Science Program
- Teva Pharmaceuticals
- Swedish Foundation for Strategic Research
- Strategic Research Center for studies on Integrative Recognition in the Immune System (IRIS), Karolinska Institute, Stockholm, Sweden
- Yeshaya Horowitz Association through the Center for Complexity Science
- ministry of Science and Technology
- Bar Ilan University
Young patients with myasthenia gravis (MG) frequently have ectopic GC in their thymus. We investigated these ectopic GC by microdissection of GC B cells and analysis of their Ig gene characteristics, in comparison to normal GC. CDR3 length distribution, a measure of clonal variability, and Ig gene family usage were similar in MG and normal tonsil samples. Lineage tree analysis demonstrated similar diversification and mutations per cell compared with normal control trees. Mutations were observed in the framework regions, responsible for the structural integrity of the BCR; however, these mutations were mostly conservative or neutral, confirming that a functional BCR is conserved in MG. In the CDR, responsible for Ag binding, selection against replacement mutations was revealed. This may indicate that the MG clones analyzed are already highly Ag-specific, and therefore potential affinity-reducing replacement mutations in the CDR3 are not propagated, due to Ag-driven selection. Somatic hypermutation (SHM) targeting motifs and aa substitution preferences in MG were similar to those of normal controls. Overall, these results suggest that B cells in the ectopic GC in MG appear to undergo normal diversification and selection, in spite of the chronic nature and different environment of the response.
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