title: Class switch recombination of the immunoglobulin heavy chain gene frequently occurs in B-cell lymphomas associated with rearrangement of the BCL2 gene.
abstract: B-cell lymphomas, mainly follicular lymphomas, carrying a t(14;18) chromosomal translocation associated with rearrangement of the BCL2 gene and the immunoglobulin heavy chain (IGH) gene, share many similarities with germinal center B cells in the secondary lymphoid follicle. In the germinal center, antigen-stimulated B cells proliferate and differentiate while undergoing isotype class switching of their immunoglobulin heavy chains. To examine whether BCL2-positive lymphoma cells show class switch recombination similar to that in the germinal center B cells, we studied the genomic configurations of the IGH gene loci in 38 patients with B-cell lymphomas. Sixteen (80%) out of 20 patients with BCL2-positive lymphomas showed class switch recombination on translocated and/or productive IGH gene loci. Lymphoma cells from 7 of the 16 patients expressed the gamma-heavy chain on their surfaces, indicating functional class switching to the gamma-constant gene on the productive allele. By contrast, 6 (33%) of the 18 patients lacking the BCL2 rearrangements exhibited class switch recombination. Statistical analysis revealed that the BCL2-positive lymphomas underwent switch recombination on either allele at a significantly higher frequency than the BCL2-negative lymphomas (P = 0.0099). This indicates that follicular lymphoma, not only morphologically but also functionally, recapitulates the germinal center. We propose that the up-regulated BCL2 expression itself is capable of playing an important role in immunoglobulin class switching.
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kadowaki
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: R
authors.initials: R
authors.lastname: Amakawa
authors.forename: T
authors.initials: T
authors.lastname: Akasaka
authors.forename: K
authors.initials: K
authors.lastname: Yabumoto
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: S
authors.initials: S
authors.lastname: Fukuhara
authors.forename: M
authors.initials: M
authors.lastname: Okuma
mesh_terms: D015321:Gene Rearrangement; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D017578:Immunoglobulin Class Switching; D016393:Lymphoma, B-Cell / Q000235:genetics*; D008224:Lymphoma, Follicular / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D014178:Translocation, Genetic
chemical_list: D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2