Somatic mutation of human immunoglobulin V genes in the X-linked hyperIgM syndrome

Y. W. Chu, E. Marin, R. Fuleihan, N. Ramesh, F. S. Rosen, R. S. Geha, R. A. Insel

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Abstract

Somatic mutation of Ig variable regions occurs prominently in germinal centers, but it has been debated whether the mutation process initiates in germinal centers or is activated before germinal center entry of B cells. We have analyzed for the presence of somatic mutation in Ig gene rearrangements of the nonpolymorphic human V(H6) gene in the X-linked HyperIgM syndrome, which is associated with defective CD40 ligand expression and absence of germinal centers and generation of memory B lymphocytes. IgM and rare IgG V(H6) productive rearrangements were isolated from PBL of patients with X- linked HyperIgM syndrome. Although the majority of both the IgM and IgG V(H6) rearrangements had a germline V(H6) sequence, 7 of 102 V(H6) IgM and I of 6 IgG rearrangements had a mutated V(H6) gene. The mutation frequency (mutations/bp) was 1.4% with a range of 2-9 mutations per clone, a mutation frequency lower, however, than that observed in IgM (3.2%) and IgG (5.4%) V(H6) rearrangements of normal individuals. These results suggest that somatic mutation may be initiated in a CD40 ligand-independent pathway before entry of B cells into germinal centers, but fails to achieve the high mutation frequency observed in the presence of germinal centers.

Original languageEnglish (US)
Pages (from-to)1389-1393
Number of pages5
JournalJournal of Clinical Investigation
Volume95
Issue number3
DOIs
StatePublished - Jan 1 1995

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Immunoglobulin Variable Region
Immunoglobulin Genes
Germinal Center
Mutation
Immunoglobulin M
Mutation Rate
Immunoglobulin G
CD40 Ligand
B-Lymphocytes
X-Linked Genes
Gene Rearrangement
Clone Cells
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Chu, Y. W. ; Marin, E. ; Fuleihan, R. ; Ramesh, N. ; Rosen, F. S. ; Geha, R. S. ; Insel, R. A. / Somatic mutation of human immunoglobulin V genes in the X-linked hyperIgM syndrome. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 3. pp. 1389-1393.
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Somatic mutation of human immunoglobulin V genes in the X-linked hyperIgM syndrome. / Chu, Y. W.; Marin, E.; Fuleihan, R.; Ramesh, N.; Rosen, F. S.; Geha, R. S.; Insel, R. A.

In: Journal of Clinical Investigation, Vol. 95, No. 3, 01.01.1995, p. 1389-1393.

Research output: Contribution to journalArticle

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