Immunoglobulin variable regions usage by B-lymphocytes infiltrating a human breast medullary carcinoma

Kotlan, Beatrix; Gruel, Nadège; Zafrani, B; Füredi, Gabrielle; Földi, J.; Petranyi, G.; Fridman, Wolf‐Herman; Teillaud, Jean‐Luc

doi:10.1016/s0165-2478(98)00098-4

Cited by 22 publications

(12 citation statements)

References 23 publications

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“…The TIL-B cells that accumulate in solid tumor tissues could be a potential source for identifying novel tumor Ags. The data presented in this work on comparing TIL-B cell Ig V region sequences at the DNA level confirm our earlier observations on the oligoclonal nature of Ig repertoire in MBC (22) and suggest that the TIL-B Ig repertoire may be Ag driven. In the defined four V H , four V, and three V families, some overrepresented clusters could be distinguished according to the tree analysis.…”

Section: Discussionsupporting

confidence: 89%

“…Escherichia coli TG1 bacteria were transformed, and positive clones were selected by PCR, as described (22,28). Sequencing of plasmid dsDNA (QIAprep Spin Miniprep kit; Qiagen) was performed partly by Sequence Version 2.0 DNA Sequencing kit (USB) and mainly by automatic sequencing (Dye Terminator Sequence Reaction Kit, DyeEx Spin kit (Qiagen; ABI PRISM Software, automatic sequencer of PerkinElmer).…”

Section: Cloning and Sequencing Of V H -J H V-j And V-j Til-b Ig Rmentioning

confidence: 99%

“…The paucity of information concerning tumor-infiltrating B (TIL-B) 3 cells has, in part, been due to the low amount of these cells found in various tumor tissues. Further studies on melanoma (17); neuroectodermal tumor (18); lung (19), ovarian (20), and colon cancer (21); and recently on breast cancer types (22)(23)(24) have shown that TIL-B cells are of potential interest. Immunocompetent B cells in some solid tumors were contributed to spontaneous tumor regression as well (25).…”

mentioning

confidence: 99%

“…Our model system for characterizing the expressed Ig repertoire (22,27,28) was established from high grade MBC because this has the highest B cell infiltration (29). A combinatorial single chain Fv (scFv) minilibrary from selected V H and V region genes was generated and tested thereafter for breast tumor cell-binding capacity.…”

mentioning

confidence: 99%

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Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes

Kotlan

Simsa²,

Teillaud

et al. 2005

The Journal of Immunology

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The potential tumor-recognizing capacity of B cells infiltrating human breast carcinoma is an important aspect of breast cancer biology. As an experimental system, we used human medullary breast carcinoma because of its heavy B lymphocytic infiltration paralleled to a relatively better prognosis. Ig-rearranged V region VH-JH, Vκ-Jκ, and Vλ-Jλ genes, amplified by RT-PCR of the infiltrating B cells, were cloned, sequenced, and subjected to a comparative DNA analysis. A combinatorial single-chain variable fragment Ab minilibrary was constructed out of randomly selected VH and Vκ clones and tested for binding activity. Our data analysis revealed that some of the VH-JH, Vκ-Jκ, and Vλ-Jλ region sequences were being assigned to clusters with oligoclonal predominance, while other characteristics of the Ab repertoire were defined also. A tumor-restricted binder clone could be selected out of the single-chain variable fragment κ minilibrary tested against membrane fractions of primary breast tumor cells and tumor cell lines, the VH of which proved to be the overexpressed VH3-1 cluster. The specific binding was confirmed by FACS analysis with primary breast carcinoma cells and MDA-MB 231 cell line. ELISA and thin layer chromatography dot-blot experiments showed this target Ag to be a ganglioside D3 (GD3). Our results are a proof of principle about the capacity of B cells infiltrating breast carcinomas to reveal key cancer-related Ags, such as the GD3. GD3-specific Abs may influence tumor cell progression and could be used for further development of diagnostic and/or therapeutic purposes.

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Section: Discussionsupporting

confidence: 89%

Section: Cloning and Sequencing Of V H -J H V-j And V-j Til-b Ig Rmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes

Kotlan

Simsa²,

Teillaud

et al. 2005

The Journal of Immunology

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“…Furthermore, a recent study demonstrated that Abs produced by TIL-B of typical medullary carcinoma (TMC) of the breast specifically bind ␤-actin, which occurs on the surface of apoptotic TMC cells in vivo (25). It has also been demonstrated that TMC TIL plasma cells are the product of intratumoral oligoclonal proliferation and differentiation (8,26). However, it is not clear that TMC is representative of other more common histologic types of breast cancer, as TMC has many unusual features, including a diagnostic plasmacytic infiltration, favorable prognosis, and expression of HLA-DR (27,28).…”

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confidence: 99%

Antigen-Driven Oligoclonal Expansion of Tumor-Infiltrating B Cells in Infiltrating Ductal Carcinoma of the Breast

Coronella

Spier

Welch

et al. 2002

The Journal of Immunology

154

124

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The objective of this study was to determine whether tumor-infiltrating B cells (TIL-B) of infiltrating ductal carcinoma (IDC) of the breast represent a tumor-specific humoral immune response. Immunohistochemical analysis of three Her-2/neu-negative IDC tumors from geriatric patients showed that TIL-B cluster in structures similar to germinal centers containing CD20+ B lymphocyte and CD3+ T lymphocyte zones with interdigitating CD21+ follicular dendritic cells, suggesting an in situ immune response. A total of 29, 31, and 58 IgG1 H chain clones was sequenced from the three IDC tumors, respectively. Intratumoral oligoclonal expansion of TIL-B was demonstrated by a preponderance (45–68%) of clonal B cells. In contrast, only 7% of tumor-draining lymph node and 0% of healthy donor PBL IgG H chains were clonal, consistent with the larger repertoires of node and peripheral populations. Patterns and levels of TIL-B IgG H chain somatic hypermutation suggested affinity maturation in intratumoral germinal centers. To examine the specificity of TIL-B Ig, a phage-displayed Fab library was generated from the TIL-B of one IDC tumor. Panning with an allogeneic breast cancer cell line enriched Fab binding to breast cancer cells, but not nonmalignant cell lines tested. However, panning with autologous tumor tissue lysate increased binding of Fab to both tumor tissue lysate and healthy breast tissue lysate. These data suggest an in situ Ag-driven oligoclonal B cell response to a variety of tumor- and breast-associated Ags.

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Genomic Applications in Breast Carcinoma

Mattos-Arruda

Weigelt

Reis‐Filho

2014

Genomic Applications in Pathology

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Immunoglobulin variable regions usage by B-lymphocytes infiltrating a human breast medullary carcinoma

Cited by 22 publications

References 23 publications

Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes

Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes

Antigen-Driven Oligoclonal Expansion of Tumor-Infiltrating B Cells in Infiltrating Ductal Carcinoma of the Breast

Genomic Applications in Breast Carcinoma

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