Ectopic GC in the thymus of myasthenia gravis patients show characteristics of normal GC

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 f...

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Bibliographic Details
Published in:European journal of immunology 2010-04, Vol.40 (4), p.1150-1161
Main Authors: Zuckerman, Neta S, Howard, Wendy A, Bismuth, Jacky, Gibson, Kate, Edelman, Hanna, Berrih-Aknin, Sonia, Dunn-Walters, Deborah, Mehr, Ramit
Format: Article
Language:English
Subjects:
Adult
Amino Acid Substitution
B-Lymphocytes - pathology
Cell Lineage
Choristoma - pathology
Clonal Deletion
DNA Mutational Analysis
Female
Genes, Immunoglobulin
Germinal Center - pathology
Humans
Hyperplasia
Immune system
Mutation
myasthenia gravis
Myasthenia Gravis - pathology
Myasthenia Gravis - surgery
Organ Specificity
Palatine Tonsil - cytology
Somatic hypermutation
Somatic Hypermutation, Immunoglobulin
Thymectomy
Thymus
Thymus Gland - pathology
Young Adult
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Summary: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.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.200939914