Ectopic B-cell clusters that infiltrate transplanted human kidneys are clonal

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 14; pp. 5560 - 5565
• Main Authors: Cheng, Julong, Torkamani, Ali, Grover, Rajesh K, Jones, Teresa M, Ruiz, Diana I, Schork, Nicholas J, Quigley, Michael M, Hall, F. Wesley, Salomon, Daniel R, Lerner, Richard A
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.04.2011; National Acad Sciences
• Subjects: allografting; Amino Acid Sequence; Antibodies; Antibodies - genetics; Antibodies - immunology; antibody libraries; B lymphocytes; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Base Sequence; Beta cells; Biological Sciences; Biopsies; Blood; Cell Movement - immunology; Cells; Chronic infection; Clone Cells - immunology; clones; Cloning; Complementarity Determining Regions - genetics; complementarity-determining region 3; Gene Expression Regulation - immunology; Genes; Genes, Immunoglobulin - immunology; Germ cells; Germinal centers; Graft rejection; Graft Rejection - immunology; Human subjects; Humans; immunoglobulin genes; Immunoglobulins; In Situ Hybridization; Kidney; Kidney - cytology; Kidney - immunology; Kidney Transplantation; Kidneys; Libraries; Lymphocytes; Lymphocytes B; Lymphoid tissue; Lymphoma; Malignancy; Molecular Sequence Data; patients; Peripheral blood; Recombination; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Transplants & implants
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1101148108

B cells and their immunoglobulin products participate in allograft rejection of transplanted human kidneys in which an interesting feature is the presence of a germinal center like B-cell clusters in the allograft. We report here that the immunoglobulin repertoires of these infiltrating B cells are highly restricted and the B cells within a cluster are clonal. Antibody libraries made from the infiltrating B cells of individual patients unexpectedly revealed that each patient utilizes a particular set of dominant germ line genes as well as dominant complementarity determining region 3. Comparison of kidney and peripheral blood from the same patient showed that the immunoglobulin genes from both compartments had dominant clones, but they differed. The lymphocytes that infiltrate the kidneys express the immunoglobulin gene somatic recombination machinery usually restricted to highly activated lymphocytes in germinal centers and lymphomas. An analogy can be made between the inescapable antigenic drive in chronic infection versus that in an allograft, both of which may lead to emergence of dominant B-cell clones and even lymphoid malignancy.