Class switch recombination was specifically targeted to immunoglobulin (Ig)G4 or IgA in Hodgkin's disease-derived cell lines

In T cell-dependent immune responses, class switch recombination occurs in germinal centres, There is now evidence that Hodgkin/Reed-Sternberg cells a re derived from germinal centre B cells, Cytokines specifically determine t he direction of class switching, i.e the isotype of the new antibodies, We performed restriction analyses and polymerase chain reaction on the immunog lobulin heavy chain loci for five Hodgkin's disease-derived B-cell lines an d one Hodgkin's disease-derived T-cell line in order to analyse class switc h recombination. In all the B-cell lines, class switch recombination had be en targeted to C alpha4 or C alpha1/2. This showed that cell-line precursor s had undergone class switching, probably under the influence of TH2 or TH3 cell-derived cytokines. Deletions comprising several constant region genes were observed in cell lines L428, L1236, L591 and KMH2. Karyotype analyses of two of these revealed translocational breakpoints within the immunoglob ulin heavy chain gene locus. Our data support the view that a chromosomal i nstability may occur during class switch recombination in Hodgkin/Reed-Ster nberg cells causing chromosomal breaks. Thus, as in other germinal centre B cell-derived lymphomas, the immunoglobulin gene locus may be frequently in volved in structural chromosomal aberrations in Hodgkin's disease.