Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. (original) (raw)

Research Article Free access | 10.1172/JCI3009

F Ghiotto, S Hashimoto, B Sellars, A Valetto, S L Allen, P Schulman, V P Vinciguerra, K Rai, L Z Rassenti, T J Kipps, G Dighiero, H W Schroeder Jr, M Ferrarini, and N Chiorazzi

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Fais, F. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Ghiotto, F. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Hashimoto, S. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Sellars, B. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Valetto, A. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Allen, S. in:[JCI](/search/results?q=author.first%5Fname%3A%22S L%22+author.last%5Fname%3A%22Allen%22&search%5Ftype=advanced) |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Schulman, P. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Vinciguerra, V. in:[JCI](/search/results?q=author.first%5Fname%3A%22V P%22+author.last%5Fname%3A%22Vinciguerra%22&search%5Ftype=advanced) |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Rai, K. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Rassenti, L. in:[JCI](/search/results?q=author.first%5Fname%3A%22L Z%22+author.last%5Fname%3A%22Rassenti%22&search%5Ftype=advanced) |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Kipps, T. in:[JCI](/search/results?q=author.first%5Fname%3A%22T J%22+author.last%5Fname%3A%22Kipps%22&search%5Ftype=advanced) |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Dighiero, G. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Schroeder, H. in:[JCI](/search/results?q=author.first%5Fname%3A%22H W%22+author.last%5Fname%3A%22Schroeder%22&search%5Ftype=advanced) |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Ferrarini, M. in:JCI |PubMed |Google Scholar

Department of Medicine, North Shore University Hospital and New York University School of Medicine, Manhasset, New York 11030, USA.

Find articles by Chiorazzi, N. in:JCI |PubMed |Google Scholar

Published October 15, 1998 -More info

Published October 15, 1998 -Version history

View PDF

Abstract

To better understand the stage(s) of differentiation reached by B-type chronic lymphocytic leukemia (B-CLL) cells and to gain insight into the potential role of antigenic stimulation in the development and diversification of these cells, we analyzed the rearranged VH genes expressed by 83 B-CLL cells (64 IgM+ and 19 non-IgM+). Our results confirm and extend the observations of a bias in the use of certain VH, D, and JH genes among B-CLL cells. In addition, they indicate that the VH genes of approximately 50% of the IgM+ B-CLL cells and approximately 75% of the non-IgM+ B-CLL cells can exhibit somatic mutations. The presence of mutation varies according to the VH family expressed by the B-CLL cell (VH3 expressers displaying more mutation than VH1 and VH4 expressers). In addition, the extent of mutation can be sizeable with approximately 32% of the IgM+ cases and approximately 68% of the non-IgM+ cases differing by > 5% from the most similar germline gene. Approximately 20% of the mutated VH genes display replacement mutations in a pattern consistent with antigen selection. However, CDR3 characteristics (D and JH gene use and association and HCDR3 length, composition, and charge) suggest that selection for distinct B cell receptors (BCR) occurs in many more B-CLL cells. Based on these data, we suggest three prototypic BCR, representing the VH genes most frequently encountered in our study. These data suggest that many B-CLL cells have been previously stimulated, placing them in the "experienced" or "memory" CD5(+) B cell subset.

Version history