Glycosylation of V region genes in follicular lymphoma as a result of the somatic hypermutation mechanism.
نویسندگان
چکیده
238 may protect against cirrhosis in homozygotes for hemochromatosis. The population studied by Fargion et al was drawn from patients who had been diagnosed clinically as having hemochromatosis. We have had the opportunity to genotype a large number of patients attending a health appraisal clinic, patients with a median age of 56 who represent the full spectrum of the phenotype associated with the homozygous state for the C282Y mutation. We found that among the 152 homozygotes detected there was a very broad range of putative disease manifestations and ferritin levels.1 If TNFgenotypes had an effect on the hemochromatosis phenotype we might expect to see it in this population. Collagen IV levels are an excellent surrogate for hepatic fibrosis in hemochromatosis,3 and, indeed, we have found that there is a slight excess of individuals with elevated collagen IV levels in homozygotes for the C282Y mutation, even among those without manifest liver disease.1 Figure 1 shows the relationship of serum collagen IV levels to TNFpromoter genotype in homozygotes for the C282Y mutation. Clearly, there is no major difference between these measurements of liver damage in the population that we have studied. Table 1 compares the serum collagen, aspartate transaminase (AST), and ferritin levels in homozygotes for the C282Y mutation with different TNFpromoter genotypes. TNFpromoter polymorphisms may be a risk factor for liver damage; if so, the effect is so small that it cannot be shown even with a group of more than 100 patients homozygous for the C282Y mutation. There must be other, more powerful, influences on the expression of the HFE mutations. So far our attempt to find such polymorphisms in the coding regions or promoters of HFE, calreticulin, 2-microglobulin, transferrin, transferrin receptor-2, DMT1 (nRamp2), ferroportin, transferrin receptor-1, IRP-1, IRP-2, hepcidin, the ferritin light and heavy chains, and ceruloplasmin have been unsuccessful. The search for genetic and environmental factors that influence the hemochromatosis phenotype must go on.
منابع مشابه
Acquisition of potential N-glycosylation sites in the immunoglobulin variable region by somatic mutation is a distinctive feature of follicular lymphoma.
Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional V(H) genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or ...
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Somatic hypermutation is the most critical mechanism underlying the diversification of Ig genes. Although mutation occurs specifically in B cells during the germinal center reaction, it remains a matter of debate whether the mutation machinery also targets non-Ig genes. We have studied mutations in the 5' noncoding region of the Bcl6 gene in different subtypes of lymphomas. We found frequent hy...
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BACKGROUND Follicular lymphoma is characterized by the t(14;18) translocation resulting in constitutive expression of BCL-2 protein; however approximately 10-15% of follicular lymphomas do not express BCL-2 protein, and a small fraction of these cases does not exhibit translocation of the BCL-2 gene either. It is highly debated whether cases of follicular lymphoma without BCL-2 gene rearrangeme...
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The expansion of follicular lymphomas (FLs) resembles, both morphologically and functionally, normal germinal center B-cell growth. The tumor cells proliferate in networks of follicular dendritic cells and are believed to be capable of somatic hypermutation and isotype switching. To investigate the relation between somatic mutation and heavy chain isotype expression, we analyzed the variable he...
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ورودعنوان ژورنال:
- Blood
دوره 100 6 شماره
صفحات -
تاریخ انتشار 2002