Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.
Although follicle center cell (FCC) lymphomas represent mature B cells, a considerable percentage do not have detectable Ig production. We have used Southern blotting and the polymerase chain reaction (PCR) to study the involvement of translocations t(14;18) and t(8;14) in causing defective Ig production in 16 Ig- FCC-derived lymphomas and three Ig- B cell acute lymphoblastic leukemias. In 6 of 19 cases, a t(14;18) was present with the other allele either deleted or in germline. In two cases a t(14;18) and a t(8;14) affected both Ig alleles, as confirmed by karyotyping. In two other cases, rearrangement of both bcl-2 on chromosome 18 and c-myc on chromosome 8 were found as well. Although cytogenetic proof was not available, the latter was probably involved in t(8;14). Restriction map analysis of one more case showed rearrangement on the pseudo-JH3 gene on one allele and t(14;18) on the other. Thus, in 11 of 19 cases, defective Ig H chain production could be explained by the inactivation of both Ig H chain genes due to translocation of one allele, in combination with deletions or defective rearrangements of the other allele. In contrast, in 28 of 30 Ig+ lymphomas, one functional Ig H chain allele was found, either in, or not in, combination with t(14;18). In two cases a single rearranged Ig H chain allele was found in combination with rearrangement of bcl-2. No comigration of the single Ig rearrangement with bcl-2, however, was found both by Southern blotting and PCR, suggesting a variant bcl-2 translocation, which leaves the Ig H chain allele functionally intact.
de Jong
D
D
Department of Pathology, University Medical Centre, Leiden, The Netherlands.
Voetdijk
B M
BM
Van Ommen
G J
GJ
Kluin-Nelemans
J C
JC
Beverstock
G C
GC
Kluin
P M
PM
D000483:Alleles; D001402:B-Lymphocytes / Q000276:immunology*; D002883:Chromosomes, Human, Pair 14; D002887:Chromosomes, Human, Pair 18; D002898:Chromosomes, Human, Pair 8; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes; D005803:Genes, Immunoglobulin; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007136:Immunoglobulins / Q000096:biosynthesis* / Q000235:genetics; D007621:Karyotyping; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000276:immunology; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D014178:Translocation, Genetic
D007143:Immunoglobulin Heavy Chains; D007136:Immunoglobulins; D004247:DNA; D004262:DNA Restriction Enzymes