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

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.

• Authors: Sazini Nzula, James J Going, David I Stott
• Journal: Cancer research (Cancer Res) Vol. 63 Issue 12 Pg. 3275-80 (Jun 15 2003) ISSN: 0008-5472 [Print] United States
• PMID: 12810659 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Immunoglobulin Variable Region

Topics

• Antibody Affinity
• Antigens, Neoplasm (immunology)
• B-Lymphocytes (immunology)
• Breast Neoplasms (immunology, pathology)
• Carcinoma, Ductal, Breast (immunology, pathology)
• Cell Division
• Cell Movement
• Clone Cells (immunology)
• Female
• Gene Rearrangement, B-Lymphocyte, Heavy Chain
• Genes, Immunoglobulin
• Humans
• Immunoglobulin Variable Region (genetics)
• Lymphocyte Activation
• Lymphocytes, Tumor-Infiltrating (immunology)
• Sequence Analysis, DNA
• Somatic Hypermutation, Immunoglobulin