Antigen-driven clonal proliferation, somatic hypermutation and selection of B-lymphocytes infiltrating human ductal breast carcinoma

Nzula, S., Going, J.J. and Stott, D.I. (2003) Antigen-driven clonal proliferation, somatic hypermutation and selection of B-lymphocytes infiltrating human ductal breast carcinoma. Cancer Research, 63(12), pp. 3275-3280.

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Abstract

Infiltration of B lymphocytes into the tumor tissue of breast cancer patients is a common occurrence, but the role of these cells in the immune response to the tumor is unknown. Heavy B-cell infiltration in medullary breast carcinoma is well documented and associated with a more favorable prognosis, implying a positive role for the humoral immune response in elimination of tumor cells. Variable B-cell infiltration has also been detected in infiltrating ductal carcinomas of the breast, but little is known about the immunoglobulin gene repertoire of these tumor-infiltrating B lymphocytes and whether they are actively responding to a local stimulus or merely passive bystanders. We have therefore investigated the repertoire of B cells infiltrating four invasive ductal carcinomas. A group of 233 rearranged Ig V-H genes was amplified, cloned, and sequenced from microdissected foci of infiltrating B cells. B cells within individual foci were polyclonal, and most were highly mutated. Several foci expressed dominant sets of V genes derived from B-cell clones. Some of these were found in more than one lymphoid cluster, indicating that B cells had migrated into the surrounding tissue and seeded new clusters. Analysis of the pattern of mutations in clonally related sets of Ig V genes expressed by tumor-infiltrating B cells shows that these cells are undergoing antigen-driven proliferation, somatic hypermutation, and affinity maturation in situ.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott I, Professor David and Going, Dr James
Authors: Nzula, S., Going, J.J., and Stott, D.I.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Cancer Research
ISSN:0008-5472

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