Abstract
e15168 Background: There is emerging evidence that inflammation plays a role in prostate carcinogenesis. To better understand the cellular biology of the immune response in prostate cancer, we investigated the immunoglobulin (Ig) repertoire of tumor-infiltrating B cells. Methods: The Ig heavy chain variable region (VH) usage reflects the antigenic experience of tumor-infiltrating B cells and may help to identify potential therapeutic targets. We analyzed IgM-VH and IgG-VH transcripts of tumor-infiltrating B cells in four tumor samples of localized prostate cancer. Immunohistochemical staining revealed groups of CD20+ B cells surrounding neoplastic prostate glands. To exclude PCR amplification bias, two cDNA librarys were prepared from separate tissue sections of each tumor. IgM-VH and IgG-VH transcripts were amplified by RT-PCR from each cDNA library, cloned and sequenced. Results: Sequencing of a total of 80 IgM-VH and 80 IgG-VH PCR products (10 IgM-VH and 10 IgG-VH PCR products from each cDNA library) revealed an oligoclonal Ig repertoire in 3 of 4 and evidence of antigen experience of B cells in 4 of 4 prostate cancer samples. IgM and IgG B cell clones, defined by the same complementarity-determining region 3 (CDR3) and detection in two separate cDNA librarys, were widely distributed in the prostate. Prostate cancer-infiltrating B cells showed somatic hypermutation, Ig class switch and insertions or deletions indicating antigen experience. Conclusions: Clonally related B cells are widely distributed in the neoplastic prostate gland suggesting the recognition of a limited number of epitopes. Future studies will identify the antigens eliciting this immune response.
Published Version
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