scholarly journals Biases in Ig λ Light Chain Rearrangements in Human Intestinal Plasma Cells

2004 ◽  
Vol 172 (4) ◽  
pp. 2360-2366 ◽  
Author(s):  
Wen Su ◽  
Laurent Boursier ◽  
Archana Padala ◽  
Jeremy D. Sanderson ◽  
Jo Spencer
1998 ◽  
Vol 187 (8) ◽  
pp. 1169-1178 ◽  
Author(s):  
Christophe Arpin ◽  
Odette de Bouteiller ◽  
Diane Razanajaona ◽  
Isabelle Fugier-Vivier ◽  
Francine Brière ◽  
...  

Human myeloma are incurable hematologic cancers of immunoglobulin-secreting plasma cells in bone marrow. Although malignant plasma cells can be almost eradicated from the patient's bone marrow by chemotherapy, drug-resistant myeloma precursor cells persist in an apparently cryptic compartment. Controversy exists as to whether myeloma precursor cells are hematopoietic stem cells, pre–B cells, germinal center (GC) B cells, circulating memory cells, or plasma blasts. This situation reflects what has been a general problem in cancer research for years: how to compare a tumor with its normal counterpart. Although several studies have demonstrated somatically mutated immunoglobulin variable region genes in multiple myeloma, it is unclear if myeloma cells are derived from GCs or post-GC memory B cells. Immunoglobulin (Ig)D-secreting myeloma have two unique immunoglobulin features, including a biased λ light chain expression and a Cμ–Cδ isotype switch. Using surface markers, we have previously isolated a population of surface IgM−IgD+CD38+ GC B cells that carry the most impressive somatic mutation in their IgV genes. Here we show that this population of GC B cells displays the two molecular features of IgD-secreting myeloma cells: a biased λ light chain expression and a Cμ–Cδ isotype switch. The demonstration of these peculiar GC B cells to differentiate into IgD-secreting plasma cells but not memory B cells both in vivo and in vitro suggests that IgD-secreting plasma and myeloma cells are derived from GCs.


Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 198-207 ◽  
Author(s):  
Hirofumi Tachibana ◽  
Hirotaka Haruta ◽  
Koji Yamada

Abstract We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original λ light chain with a new λ chain (light chain shifting) at a high rate. Loss of the original rearranged λ light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new λ chain, which replaces the original λ chain, occurs by rearranging new VJ segments on a previously excluded allele. V λ gene usage of these new rearrangements are biased toward Vλ4, Vλ6, and Vλ10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new λ chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.


Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 836-839 ◽  
Author(s):  
Daijiro Abe ◽  
Chiaki Nakaseko ◽  
Masahiro Takeuchi ◽  
Hiroaki Tanaka ◽  
Chikako Ohwada ◽  
...  

Abstract POEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially λ-restricted. Here we determined complete nucleotide sequences of monoclonal immunoglobulin λ light chain (IGL) variable regions in 11 patients with POEMS syndrome. The V-region of the Igλ gene of all 11 patients was restricted to the Vλ1 subfamily. Searching for homologies with IGL germlines revealed that 2 germlines, IGLV1-44*01 (9/11) and IGLV1-40*01 (2/10), were identified, with an average homology of 91.1%. The IGLJ3*02 gene was used in 11 of 11 re-arrangements with an average homology of 92.2%. These data suggest that the highly restricted use of IGL Vλ1 germlines plays an important role in the pathogenesis of POEMS syndrome.


Author(s):  
Saeko Yamada ◽  
Hiroko Kanda ◽  
Hiroyuki Abe ◽  
Yukako Shintani Domoto ◽  
Ryochi Yoshida ◽  
...  

Abstract Overlap syndrome refers to a group of conditions that have clinical features of more than one well-characterized rheumatic disease and meet the respective classification criteria. There are no typical renal histological findings in overlap syndrome. When patients with overlap syndrome develop renal dysfunction, various potential causes, including lupus nephritis (LN), renal crisis by systemic sclerosis, interstitial nephritis and so on, need to be distinguished. Here we report a 44-year-old woman with overlap syndrome involving systemic lupus erythematosus (SLE), diffuse cutaneous systemic scleroderma and Sjogren’s syndrome, who was also positive for anti-mitochondrial M2 antibody. She developed glomerular hematuria, proteinuria and increase in creatinine appeared gradually. Suspecting lupus nephritis, renal biopsy was performed. However, in the interstitium, mild infiltration of lymphocytes and plasma cells and very partial fibrosis were observed. Immunofluorescence (IF) microscopy revealed predominant mesangial IgM, C3 and λ light chain staining. Overall, LN was not diagnosed based on these findings. Renal dysfunction was normalized by glucocorticoid treatment for three months. This case suggests the importance of a renal diagnosis based on renal pathological findings, especially in a case of overlap syndrome including SLE.


Blood ◽  
1999 ◽  
Vol 93 (1) ◽  
pp. 198-207
Author(s):  
Hirofumi Tachibana ◽  
Hirotaka Haruta ◽  
Koji Yamada

We identified an antibody-secreting human B-cell line (HTD8), which actively replaces the production of the original λ light chain with a new λ chain (light chain shifting) at a high rate. Loss of the original rearranged λ light chain occurs by significantly reducing the amount of transcript expressed. Expression of the new λ chain, which replaces the original λ chain, occurs by rearranging new VJ segments on a previously excluded allele. V λ gene usage of these new rearrangements are biased toward Vλ4, Vλ6, and Vλ10 families, which are known to be the least frequently used. In striking contrast to the plasma cell phenotype, recombination activating genes, RAG-1 and RAG-2, were expressed in the HTD8 cells and were shown to be necessary, but insufficient for inducing expression of the new λ chain. These results suggest that human plasma cells have the potential to actively undergo light chain replacement.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5342-5342
Author(s):  
Yang Hu ◽  
Mangju Wang ◽  
Yan Chen ◽  
Xue Chen ◽  
Fang Fang ◽  
...  

Abstract In this study we analyzed the immunophenotype characteristics of the plasma cells and evaluated the significance of the abnormal plasma cell clone in bone marrow in primary systemic light chain amyloidosis (AL) patients. Fresh bone marrow samples were collected from 74 cases of plasma cell disease (PCD), including 51 cases of AL, 21 cases of multiple myeloma (MM), 2 cases of Waldenström's macroglobulinemia (WM). All patients diagnosed according to WHO 2008 diagnostic criteria. The diagnosis of AL was confirmed by the presence of monoclonal immunoglobulin or free light chain in blood or urine, and/or amyloidosis in fat tissues or biopsies by Congo red staining. Ten healthy donors were also collected as controls. Their clinical characteristics and immunophenotype of bone marrow cells were compared and analyzed. The immunophenotype were analyzed with a panel of antibodies including CD45, CD38, CD138, CD117, CD56, CD19, CD20, Igκ, Igλ, CD7, CD22, CD3, CD34 and CD27 by flow cytometry (FCM). The results were for statistical processing. The prominent feature of AL patients was multi-organ and multi-system involvement. Kidney was the major organ involvement (82.4%), followed by cardiovascular system (58.8%); MM mainly had the clinical manifestations of bone lesions (85.7%) and renal involvement (47.6%). The serum immunoglobulin of AL mainly manifested as λ light chain (74.5%), while the majority of MM manifested as κ (61.9%). In the 51 patients of AL, the ratio of plasma cellsin bone marrow was mean 3.87% (0.17∼9.34%) by FCM, and 4.47% (0∼14.5%) by morphological examination. In MM, the ratio of plasma cells was mean 13.17% (1.30∼48.91%) by FCM and 33.55% (3.0∼81.5%) by morphological examination. The plasma cells proportion between AL and MM had significant difference (P< 0.05). The κ or λ light chain restriction can be used for the detection of abnormal plasma cell clones in AL patients. The κ/λ ratio>4.0 or <0.5 can be used as the criteria to identify light chain restriction in plasma cells in AL patients. The 31/51 cases of AL could detected abnormal plasma cell clone that used κ/λ light chain restriction and were mainly expressed λ light chain (24/31, 77.4%). The 21 cases of MM had light chain restriction, mainly expressed κ light chain (13/21, 61.9%) (P<0.05). In CD45/SSC scattergram, the position of abnormal plasma cells of AL patients varied in a wider range. According to the features of CD38+/CD138+ as the basic markers for plasma cells, abnormal plasma cells were CD45 negative or weak positive in AL patients, similar to the CD45 level distribution in malignant plasma cells in MM. In WM, the proliferated cells were plasmacytoid lymphocytes with CD45 weakly or strong positive. FCM can identify abnormal plasma cell clone in bone marrow of AL patients. In 51cases of AL, 78.4% of bone marrow plasma cells were CD56+, 68.6% were CD117+, and 88.2% were CD19-. In 21 of MM, 66.7% were CD56+, 38.1% were CD117+, and 90.4% were CD19-. These results manifested significant difference compared with those of normal plasma cells (P< 0.05). In 2 cases of WM, these plasmacytoid lymphocytes were CD19+ and CD56-, CD117-.The ratios of CD56+, CD117+, CD19-, and CD45-/dim in bone marrow plasma cells were significantly higher in AL patients than in WM patients and healthy individuals (P<0.05), but were similar to those in MM patients (P>0.05). The main difference between AL and MM was the larger size of plasma cell group in MM (P<0.05). In summary, according to light chain restricted expression and abnormal immunephenotype by FCM analysis we can determine abnormal plasma cell clone in bone marrow of AL patients and the abnormal plasma cells clone can be used as an important diagnostic marker of AL. Disclosures: No relevant conflicts of interest to declare.


2003 ◽  
Vol 15 (2) ◽  
pp. 166-169 ◽  
Author(s):  
Mamoru Kameyama ◽  
Yoshiharu Ishikawa ◽  
Tomoyuki Shibahara ◽  
Koichi Kadota

A diagnosis of plasma cell myeloma was made in a 6-year-old Holstein cow that showed continuous nosebleed, progressing emaciation, and hyperglobulinemia. Necropsy revealed enlargement of the caudal mesenteric lymph nodes. Lymph nodes and spleen were infiltrated by neoplastic plasma cells. Renal lymph nodes, bone marrow, and kidneys also were affected. Amyloid-like material that was negative for Congo red was present in most of the affected lymph nodes. Congo red–positive amyloid material was noted in spleen, kidneys, liver, and adrenal glands. Neoplastic plasma cells exhibited immunohistochemical reactions for λ-light chain and 3 classes of heavy chain but not for κ-light chain. Nonamyloid deposits were labeled with antisera against λ-light chain and heavy chains. Plasmacytoid cells, which stained positively for IgG, IgM, or IgA, were intermingled in all lesions. Production of 3 types of immunoglobulins may be caused by heavy-chain class switching, constantly occurring in certain proportions.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5184-5184
Author(s):  
Juan Li ◽  
Shao-Kai Luo ◽  
Ying Zhao

Abstract Multiple myeloma is still an incurable malignancy with low complete remission rate and a high recurrence rate by conventional therapy. The fludarabine-based regimen of eliminating the B lymphocytes may reduce or suppress the relapse of multiple myeloma. We treated the patients with relapsed and refractory multiple myeloma with FMD (fludarabine 35 mg/m2/d, d1~3, mitoxantrone 8 mg/m2/d, d1 and dexamethasone 20mg/d, d1~4). The results are encouraging. Case one: A 47 year-old female presented with lumbosacral pain (for 2 months), dull pain in the low back, palpitations, distress, and shortness of breath. Her peripheral blood examination showed that her white blood cell (WBC) count was 5.71×109/L, the hemoglobin concentration was 81 g/L and the platelet count was 181×109/L. The serum IgG was 118.0g/L, λ light chain was 115.84 g/L, globulin was 133 g/L, albumin was 26 g/L, and β2-MG was 3491.8 μg/L. The serum Ca2+ was 2.2 mmol/L. The urine Bence-Jones protein electrophoresis was negative. The immunoelectrophoretic analysis showed a monoclonal protein: IgG-lambda. A bone marrow aspirate revealed 38% plasma cells. The body bone radiograph revealed generalized osteoporosis and depressed fracture of L2 and L4. She was diagnosed as Multiple Myeloma. The patient subsequently began 5 courses of VADM every 4 weeks (vincristine 0.5 mg on Days 1–4, THP 10 mg on Days 1–4, dexamethasone 20 mg on Days 1–4, Melphan 6 mg BID on Days 1–4). The lumbodynia was relieved after chemotherapy. But after 5 courses of VADM, her hemoglobin level was 81 g/L, IgG was 40.9 g/L, λ light chain was 33.28 g/L, albumin was 56 g/L, and β2-MG was 2156.2 μg/L. A BM study showed 30% plasma cells. The body bone radiograph was the same as before. Then she was treated with 3 courses of FMD. The symptoms of lumbodynia were relieved. A bone marrow study showed 14% plasma cells. The hemoglobin level was 125 g/L, IgG was 21.9 g/L, λ light chain was 31.3 g/L, albumin was 63 g/L, and β2-MG was 1670.6 μg/L. No more new lytic lesion appeared. There were no obvious side effects during the treatment. Case two: A 57-year-old male presented with shortness of breath, palpitations caused by hard work and pain of the lower back, which had been continuing for 4 months. Prior to his admission, the bone marrow showed a 19.5% plasma cells. The immunoelectrophoretic analysis disclosed the presence of a monoclonal component of IgA-kappa protein. Serum levels of immunoglobulin were 7.45 g/L for IgA and 15.04 g/L for kappa. Serum creatinine was 123 mmol/L, BUN 5.2 mmol/L, calcium 2.3 mmol/L, β2-microglobulin 6114.5 mg/L and hemoglobin was 61 g/L. The bone X-ray showed generalized osteoporosis and depressed fracture of L2 and L4. The patient was diagnosed as multiple myeloma and received 2 cycles of M2 and 2 cycles of VAD. But his symptoms did not improve and pain increased. After admission, the BM smear showed plasma cells of 46%. Serum IgA was 9.91 g/L, kappa was 17.79 g/L, calcium was 2.5 mmol/L, β2-microglobulin was 3338.8 mg/L, and hemoglobin was 84 g/L. The patient was given treatment with the regimen of FMD, repeated every 4 weeks. Four months later, after the 3 cycles of FMD were administered, the BM showed only 16% of plasma cells in smear specimen. Serum IgA was 8.25 g/L, kappa was 8.39 g/L, creatinine was 103 mmol/L, BUN was 7.0 mmol/L, calcium was 2.2 mmol/L, β2-microglobulin was 2926.0 mg/L, and hemoglobin was 112 g/L. The bone X-ray did not show new lytic lesions. So far 8 months after finishing 8 cycles of FMD, the patient was in a good condition and had no bone pain.


2021 ◽  
pp. 106689692110082
Author(s):  
Sarah Al-Rawaf ◽  
Salem Alowami ◽  
Robert Riddell ◽  
Asghar Naqvi

Russell bodies are accumulation of immunoglobulin in plasma cells forming intracytoplasmic inclusions. Russell body colitis is rare with only 3 cases described in the English literature up to date. We report a 78-year-old male with cirrhosis showing prominent cecal infiltration of Russell body containing plasma cells. Plasma cells showed no nuclear atypia or mitoses, and no evidence of light chain restriction. In this article, we report a fourth case of Russell body colitis, that is unique in being localized to the cecum in contrast to the other 3, 1 of which was in an inflammatory polyp in the sigmoid colon, 1 in a rectal tubulovillous adenoma and 1 as part of diffuse gastrointestinal disease. This is therefore the first report of localized Russell body typhlitis, occurring in a cirrhotic patient in whom an adjacent erosion was likely nonsteroidal anti-inflammatory drug-associated, a combination that may have facilitated the formation of Russell bodies.


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