| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037
Tumor-infiltrating lymphoplasmacytic cells are a key feature of medullary carcinoma of the breast (MCB), a distinct subtype of human breast cancer that, despite cytologically anaplastic characteristics, has a more favorable prognosis than other types of breast cancer. Since it has been proposed that the improved clinical outcome is due at least in part to the presence of a prominent lymphoplasmacytic cell infiltrate in the tumor stroma, we recently examined the tumor-infiltrating B cell response in MCB and showed that it is oligoclonal and directed against an intracellular protein translocated to the cell surface upon MCB cell apoptosis. Human Abs cloned from MCB lymphoplasmacytic infiltrate-derived phage display libraries and reflecting the dominant part of the response were used to identify the target Ag as actin. Here, we have characterized in detail the cloned human IgG Abs and the translocation process of actin to the cell surface of apoptotic MCB cells. Our analysis shows that the cloned Abs bind specifically and with high affinity to actin, as determined by ELISA and surface plasmon resonance. Sequence analysis revealed that the Abs are highly somatically mutated, with high replacement to silent ratios, indicative of an Ag-driven, affinity-matured response. Interestingly, the tumor-infiltrating B cells in half the MCB patients mainly exhibited an IgG2 response, while IgG1 dominated in the others. To gain insight to the molecular events that may elicit such an Ab response, we examined the translocation of actin to the cell surface of apoptotic MCB cells using flow cytometry and laser scanning cytometry. Our results show that actin becomes exposed on the cell surface of a large proportion of apoptotic MCB cells as an early apoptotic event. We propose that the Ab response against actin produced by tumor-infiltrating B lymphoplasmacytic cells is Ag-driven, affinity-matured, and elicited due to the increased rate of apoptosis occurring within the MCB tumor that facilitates the translocation and proteolytic fragmentation of intracellular proteins.
This article has been cited by other articles:
|
|
 |
|
  L. de la Cruz-Merino, E. Grande-Pulido, A. Albero-Tamarit, and M. E. Codes-Manuel de Villena Cancer and Immune Response: Old and New Evidence for Future Challenges Oncologist, December 1, 2008; 13(12): 1246 - 1254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schmidt, D. Bohm, C. von Torne, E. Steiner, A. Puhl, H. Pilch, H.-A. Lehr, J. G. Hengstler, H. Kolbl, and M. Gehrmann The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer Cancer Res., July 1, 2008; 68(13): 5405 - 5413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Bertucci, P. Finetti, N. Cervera, E. Charafe-Jauffret, E. Mamessier, J. Adelaide, S. Debono, G. Houvenaeghel, D. Maraninchi, P. Viens, et al. Gene Expression Profiling Shows Medullary Breast Cancer Is a Subgroup of Basal Breast Cancers. Cancer Res., May 1, 2006; 66(9): 4636 - 4644. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Kotlan, P. Simsa, J.-L. Teillaud, W. H. Fridman, J. Toth, M. McKnight, and M. C. Glassy Novel Ganglioside Antigen Identified by B Cells in Human Medullary Breast Carcinomas: The Proof of Principle Concerning the Tumor-Infiltrating B Lymphocytes J. Immunol., August 15, 2005; 175(4): 2278 - 2285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Nzula, J. J. Going, and D. I. Stott Antigen-driven Clonal Proliferation, Somatic Hypermutation, and Selection of B Lymphocytes Infiltrating Human Ductal Breast Carcinomas Cancer Res., June 15, 2003; 63(12): 3275 - 3280. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
