Salivary gland B cell lymphoproliferative disorders in Sjögren's syndrome present a restricted use of antigen receptor gene segments similar to those used by hepatitis C virus-associated non-Hodgkins's lymphomas

Re, Vallì De; Vita, Salvatore De; Gasparotto, Daniela; Marzotto, A.; Carbone, Antonino; Ferraccioli, Gianfranco; Boiocchi, Mauro

doi:10.1002/1521-4141(200203)32:3<903::aid-immu903>3.0.co;2-d

Cited by 98 publications

(93 citation statements)

References 45 publications

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“…Analyses of RFs in MC-II and in donors immunized with mismatched RBCs revealed four groups of stereotyped immunoglobulin (Ig) V H -D H -J H rearrangements, each with distinct heavy-chain complementary-determining region 3 (HCDR3) amino acid sequences: two with IGHV1-69/JH4 rearrangements, designated V1-69-RF and RF-WOL, and two with IGHV3-7/JH3 and IGHV4-59/JH2 rearrangements, designated V3-7-RF and V4-59-RF, respectively. [2][3][4] Remarkably, similar stereotyped RF-rearrangements are frequently expressed in malignant B-cell lymphomas. 2,5,6 Previously, we have shown that recombinantly produced V1-69-RF, V3-7-RF and RF-WOL, derived from gastric and salivary gland marginal zone B-cell lymphomas (MZBCL), bind with high-affinity to IgG in vitro.…”

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confidence: 80%

A novel chronic lymphocytic leukemia subset expressing mutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient

et al. 2012

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Rheumatoid factors (RFs) are auto-antibodies, mostly of the IgM isotype, that specifically bind to the Fc portion of IgG. RFs are transiently produced in healthy individuals in response to infections and after immunization with mismatched red blood cells (RBCs). RFs are chronically produced in patients suffering from rheumatoid arthritis, Sjö gren's syndrome and in hepatitis C virus (HCV)-induced type-II mixed cryoglobulinemia (MC-II) (reviewed in Newkirk 1 ). Analyses of RFs in MC-II and in donors immunized with mismatched RBCs revealed four groups of stereotyped immunoglobulin (Ig) V H -D H -J H rearrangements, each with distinct heavy-chain complementary-determining region 3 (HCDR3) amino acid sequences: two with IGHV1-69/JH4 rearrangements, designated V1-69-RF and RF-WOL, and two with IGHV3-7/JH3 and IGHV4-59/JH2 rearrangements, designated V3-7-RF and V4-59-RF, respectively. [2][3][4] Remarkably, similar stereotyped RF-rearrangements are frequently expressed in malignant B-cell lymphomas. 2,5,6 Previously, we have shown that recombinantly produced V1-69-RF, V3-7-RF and RF-WOL, derived from gastric and salivary gland marginal zone B-cell lymphomas (MZBCL), bind with high-affinity to IgG in vitro. 2,7 V1-69-RF, V3-7-RF, RF-WOL and V4-59-RF rearrangements are also frequently expressed in HCV-associated lymphomas, splenic marginal zone lymphomas and in individual cases of ocular MZBCLs and diffuse-large B-cell lymphomas. 5,6,[8][9][10] Recently, Kostareli et al. 10 reported 12 cases of B-cell chronic lymphocytic leukemia (CLL) expressing V4-59-RF and Fazi et al. 11 reported two cases of V3-7-RF in monoclonal B-cell lymphocytosis.In this study, we analyzed HCDR3 amino acid sequences of 81 IGHV3-7-expressing CLL and identified 3 cases with strong homology to 25 previously reported V3-7-RFs from both healthy and malignant B-cells (Table 1, Supplementary Table 1). These 25 V3-7-RF cases include 9 with proven RF-activity in vitro. The three newly found CLL cases, CLL81, CLL311 and CLL416, utilized the IGHD3-22 gene segment and the IGHJ3 segment shared by 15/24 and 22/24 of V3-7-RFs, respectively. The CLL V3-7-RFs displayed 470% of homology with a V3-7-RF HCDR3 consensus sequence, defined by the amino acids used by the majority of V3-7-RF cases (Table 1). Of note, the V3-7-RFs also shared amino acids encoded by non-templated N-region nucleotides (Figure 1a). Two of the newly identified CLL V3-7-RF cases (CLL81 and CLL416) expressed the stereotyped IGKV3-15 Ig light chain (IgV L ) reported in 10/10 V3-7-RF cases (Table 1). In CLL311, the V3-7-RF Ig heavy chain (IgV H ) was paired with an IGKV3-20-encoded IgV L . Remarkably, similar IGKV3-20 rearrangements were found in the other groups of stereotyped RFs.The CLL V3-7-RFs were heavily mutated (94.5±1.9% average homology to the IGHV3-7 germline) and shared replacement mutations Q58P, Y66F and Q90E (Figure 1a and Supplementary Table S2). Identical somatic mutations are also frequent among

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confidence: 80%

A novel chronic lymphocytic leukemia subset expressing mutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient

et al. 2012

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“…13 were also tested using ELISA and none displayed RF activity, to further prove the specificity of our findings with the mAb from patient IT01-0199. 10,12 The subset of CLL cases reported here (subset no. 13) is defined by the expression of mutated stereotyped IGHV4-59/IGKV3-20 mIG, suggesting strong selection of B cells with unique molecular features within their antigen-binding sites.…”

Section: Rearrangements (Supplementarymentioning

confidence: 99%

“…The percent bound was calculated by using the optical density (OD), taking the OD without a competitor as 100% bound. Tables 3 --5) from: (1) two cases (GR-02-0006 and UK-02-0067) classified as atypical CLL (both CD23À and CCND1/IGHÀ by fluorescence in situ hybridization); HCV serology data were available for one case that was found positive for anti-HCV antibodies; (2) two cases (505-12609 and DK-01-0114) with SMZL, both positive for anti-HCV antibodies; (3) a case of CLL-like monoclonal B-cell lymphocytosis (MBL) from our published series 9 (case 89Vb), also HCV seropositive; (4) two cases with SS-associated monoclonal myoepithelial sialadenitis (SS-MESA) from the public database (cases 7 and 11 in De Re et al 10 ; GEDI: AF303917 and GEDI: AF303914). The stereotyped VH domains in both CLL and non-CLL cases, carried a distinctive CDR3 created by the association of the IGHV4-59, IGHD2-15 and IGHJ2 genes.…”

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Antigen receptor stereotypy across B-cell lymphoproliferations: the case of IGHV4-59/IGKV3-20 receptors with rheumatoid factor activity

et al. 2011

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“…Several studies demonstrated infact the presence of IgV genes mutations compatible with a germinal center (GC) or post-GC derivation, a replacement/silent mutation ratio consistent with the maintenance of a functional structure of the BCR, and the presence of intraclonal heterogeneity. 4,5,13,14 These notions are further strongly supported by the observation that a proportion of HCV-related MC and NHL are curable by virus eradication. [15][16][17][18][19] Conceivably, the similarity in the structure of the variable BCR region may account for selection of B cells expressing specific and common reactivity.…”

Section: Introductionmentioning

confidence: 99%

HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations

Sansonno

Simula

et al. 2006

Leukemia

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We demonstrate that in three cases of MC (two with immunocytoma), the IgM-RF þ component of their cryoprecipitated represents the circulating counterpart of the B-cell receptor (BCR) of the monoclonal overexpanded B-cell population. These IgMs were isolated and used to demonstrate a crossreactivity against both hepatitis C virus (HCV) NS3 antigen and the Fc portion of IgG. Epitopes were identified in a fraction of exemplary samples by using epitope excision approach (NS 31250-1334 and IgG Fc 345-355 ). The same phenomenon of crossreactivity has been shown to occur in vivo after immunization of a mouse with the NS3 1251À1270 peptide. To verify if the same reaction was also present in MC samples characterized by an oligo/polyclonal B-cell proliferation, IgM crossreactivity was tested in 14 additional samples. Five out of the 14 were reactive against HCV NS3 and 11 out of 14 were reactive against IgG-Fc peptide. The data support the role of HCV NS3 antigen in a subset of patients with MC, whereas the high frequency of the IgG-Fc epitope suggests that these B cells originate from precursors strongly selected for auto-IgG specificity. We suggest that engagement of specific BCRs by NS3 (or NS3-immunocomplex) antigen could explain the prevalence of IgM cryoglobulins in these patients

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Salivary gland B cell lymphoproliferative disorders in Sjögren's syndrome present a restricted use of antigen receptor gene segments similar to those used by hepatitis C virus-associated non-Hodgkins's lymphomas

Cited by 98 publications

References 45 publications

A novel chronic lymphocytic leukemia subset expressing mutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient

A novel chronic lymphocytic leukemia subset expressing mutated IGHV3-7-encoded rheumatoid factor B-cell receptors that are functionally proficient

Antigen receptor stereotypy across B-cell lymphoproliferations: the case of IGHV4-59/IGKV3-20 receptors with rheumatoid factor activity

HCV-NS3 and IgG-Fc crossreactive IgM in patients with type II mixed cryoglobulinemia and B-cell clonal proliferations

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