Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the molecular characterization of 2A4, an IgG, DNA-binding antibody bearing the 3I and F4 idiotypes which are associated with anti-DNA antibodies in serum of patients with systemic lupus erythematosus (SLE). The antibody is produced by an EBV-transformed B cell line derived from a patient with multiple myeloma whose myeloma protein is also an IgG, 3I-reactive, F4-reactive, DNA-binding immunoglobulin, although the 2A4 antibody does not itself represent the myeloma protein. The 2A4 heavy chain is encoded by a VH4 gene, a D-D gene fusion and the JH6 gene; the light chain is derived from a Vk1 gene and the Jk2 gene. This is the first human antibody shown to have a CDR3 encoded by a D-D fusion. DNA sequence analysis of the 2A4 VH gene together with a Southern blot of genomic DNA probed with a 2A4 VH-specific oligonucleotide strongly suggest it to be somatically mutated. The data provide evidence that human autoantibodies can be products of somatically mutated genes and suggest that the 2A4 antibody may reflect the selective pressure of antigen.
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PMID:Molecular characterization of a somatically mutated anti-DNA antibody bearing two systemic lupus erythematosus-related idiotypes. 211 Jan 88

We determined the specificity and sequence of immunoglobulin molecules synthesized by monoclonal B cells from a patient with chronic lymphocytic leukaemia (CLL) who presented with a number of clinical and biological autoimmune symptoms. Heterohybrids obtained by fusion of CLL cells with the mouse X63-Ag 8.653 myeloma produced IgM lambda MoAbs directed to the cardiolipin/beta 2 glycoprotein I (beta 2GPI) complex and ssDNA. They were devoid of polyreactivity. Nucleotide sequence analysis of the variable domain of the mu chain indicated the utilization of the VH4 71.2 gene or one allotypic variant, DXP4 and JH3 segments. The lambda light chain used the single gene from the V lambda 8 subfamily, J lambda 3 and C lambda 3 genes. The VH gene displayed 11 nucleotide changes in comparison with its putative germline counterpart. However, these nucleotide changes correspond to variations observed in other published VH4 sequences, suggesting gene polymorphism rather than somatic mutation. DXP4 and JH3 were also in germline configuration. The VL gene exhibited a single replacement mutation in CDR1. These data suggest that the monoclonal CLL B cells in this patient retained VH and VL genes in germline configuration although they secreted a pathogenic anti-cardiolipin antibody associated with clinical symptoms, vasculitis and thrombosis, which may be provoked by antibodies to the phospholipid/beta 2GPI complex.
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PMID:Characterization of a human monoclonal autoantibody directed to cardiolipin/beta 2 glycoprotein I produced by chronic lymphocytic leukaemia B cells. 822 31

GM 4672 is an IgG2 kappa-producing lymphoblastoid cell line derived from a patient with multiple myeloma. It has been used by many laboratories as a fusion partner for the production of human-human hybridoma monoclonal antibodies. GM 4672 immunoglobulin variable region heavy and light chain family usage was originally assigned to VH1 and VK1, respectively. This assignment was based on the positions of [3H]leucine of the heavy and light chain proteins using the Edman degradation method. Using the polymerase chain reaction and variable region leader primers and constant region primers, we report here the immunoglobulin variable region gene sequence expressed by GM 4672. The VH region belongs to the VH4 family and is most homologous with the V71-2 (87.9%), DK1, and JH4 germline genes. The entire heavy chain V region contained 41 mutations in 36 codons and included 11 N nucleotide additions flanking the D region. GM 4672 VK region contained a VK1 gene rearranged with a JK4 gene. The VK germline gene used by GM 4672 light chain was not identified but showed the most homology with Vb' germline gene (87.7%). When compared to Vb' and JK4 genes, there were 37 mutations in 30 codons with evidence of antigen selection as determined by the replacement to silent mutation ratio in the complementarity-determining regions. The high frequency of mutations in the V region genes of GM 4672 is comparable to the sequences of other myeloma proteins.
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PMID:Immunoglobulin V region heavy and light chain gene sequences of the lymphoblastoid cell line GM 4672. 835 59

The immunoglobin heavy chain variable region (VH) gene usage in multiple myeloma (MM) has not been reported, although a few studies have incidentally identified the VH gene rearranged in small cohorts of MM patients. We used a reverse transcriptase-polymerase chain reaction based technique to analyze the VH gene usage in MM. The VH sequences were obtained after amplification of bone marrow cDNA using the seven VH family-specific and constant region primers. The VH sequences of 72 patients were successfully identified. The frequency of VH family usage in decreasing order was VH3>VH4>VH1>VH5>VH2>VH6>VH7 and corresponded to the functional germline complexity of the VH families. Individual VH genes (VH1-69, VH3-9, VH3-23, and VH3-30) were overrepresented in our cohort of MM patients; some VH genes [VH3-49, VH3-53, and VH4.21 (VH4-34)], which are rearranged with increased frequency in normal circulating B cells, autoimmune diseases, and other B-cell malignancies, were not detected in any MM patient. Compared with germline sequences, an average of 8.8% (range, 2.7% to 16.5%) of the nucleotides had evidence of mutation within each VH sequence. Based on these results, we conclude that (1) the VH gene usage in MM is unique compared with other malignant and nonmalignant B-cell populations, (2) the physiologic process of clonal deletion functions to remove clones that have rearranged VH genes (VH4.21) capable of expressing antibodies, which recognize self-antigens, and (3) the complete lack of VH4.21 gene rearrangement may help to partially explain the paucity of autoimmune phenomena in MM.
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PMID:VH gene usage is multiple myeloma: complete absence of the VH4.21 (VH4-34) gene. 863 3

We have analyzed the immunoglobulin heavy chain (VH) gene variable regions (CDR2 and FW3) of 101 Japanese cases with peripheral B cell neoplasms. When all except one case with a deletion were graphed by frequency of replacement mutation, the 100 cases could be separated into two groups: 24 cases with zero, one and two mutations (germline or low frequency of somatic mutation); and 76 cases with three or more mutations (medium to high frequency of somatic mutation). While most mantle cell lymphoma cases (11/13) showed germline or low frequency of somatic mutation, all cases of mucosa-associated lymphoid tissue (MALT) lymphoma (11/11), follicular lymphoma (three of three cases), plasma cell myeloma (seven of seven cases) and most cases of diffuse large B cell lymphoma (DLBCL; 42/47) belonged to the latter group. These 76 cases, therefore, may be considered to show somatic hypermutation. More than half of chronic lymphocytic leukemia/small lymphocytic lymphoma cases (CLL/SLL; eight of 13) showed a hypermutated VH gene and the ratio of replacement mutation: silent mutation in CDR2 of CLL/SLL was considerably higher compared with DLBCL and MALT lymphoma, showing somatic hypermutation. When comparing VH gene type of B cell-CLL (B-CLL) among our series and those in the literature, more cases of CD5+ B-CLL in the Western literature have the VH5 and VH6 family types, while more cases in Japan are reported to have VH4 family. The occurrence of VH families in B-CLL between Japanese and Western people seems to be comparable.
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PMID:Analysis of the immunoglobulin heavy chain gene variable region of 101 cases with peripheral B cell neoplasms and B cell chronic lymphocytic leukemia in the japanese population. 1050 19