![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
Abstract
Non-Hodgkin's B-lymphomas (B-NHL) are a very heterogeneous group of B-cell neoplasias originating from the germinal centers of lymphatic follicles. Thus, they represent a suitable experimental model to study the molecular basis of certain key events which take place in the lymphatic follicles, including somatic hypermutation and heavy chain isotypic switch.
An unusual B-NHL cell line (“Farage”) not producing Ig polypeptide chains was previously shown to rearrange its IgH and Ig genes and transcribe seemingly normal size μ and mRNAs. In an attempt to characterize the phenotype of Farage cells better and to elucidate the molecular basis of the failure of Farage cells to synthesize Ig chains, we sequenced its VH and VK rearranged gene segments by PCR and RT-PCR. It was found that both V genes are somatically, heavily mutated compared to their germline counterparts. In addition, this rearranged VDJ gene of the heavy chain is not transcribed. Instead, the Farage cells express a low level of a new family of germline transcripts starting with a VH like sequence, continuing with a small segment of the 3VH germline flanking region, and ending within the Cμ region. These transcripts lack D and J segments and do not contain the open reading frame of the full-length Cμ protein. Thus, Farage cells fail to produce μ heavy chains due to silencing of the expression of the conventional VDJCμ transcript and expression of unusual Cμ-germline transcripts. In contrast to the IgH genes, the rearranged VJ gene of Farage is transcribed and gives rise to a full-size -mRNA. This transcript, however, is not translated to a full-length -chain, as it contains a stop codon in its coding region. All the above show that Farage cells are unable to produce Ig polypeptide chains, due to somatic mutations altering the -chain gene, and mutations and/or regulatory events that shutoff the transcription of the IgH gene.
The heavily mutated VK and VH genes found, support the conclusion that the Farage cell line originated either from germinal center cells or from the mantle zone of the lymphoid follicle.