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Identification of Common Germinal-Center B-Cell Precursors in Two Patients with Both Hodgkin's Disease and Non-Hodgkin's Lymphoma

Brauninger A, Hansmann ML, Strickler JG, Dummer R, Burg G, Rajewsky K, Kuppers R
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

Reviewers: Kenneth Blank, MD
Source: New England Journal of Medicine Vol. 340 No. 16 p. 1239

Introduction

B-cells are immune cells that fight infection by producing immunoglobulins, a type of protein on the surface ofB-cells, which binds to antigens. Each B-cell has a unique immunoglobulin that is formed from three differentgenes: the variable gene (V gene), the diversity gene (D gene) and the joining gene (J gene).

Some investigators believe that Hodgkin's disease and non-Hodgkin's lymphoma arise when B-cells becomecancerous. However, other investigators argue that Hodgkin's Disease develop when other cells becomecancerous, namely, monocytes or dendritic cells. Given the uniqueness of B-cells' immunoglobulin,investigators from Germany examined the immunoglobulin genes in the tumor cells of two patients, each withHodgkin's disease and non-Hodgkin's lymphoma, to determine the role of B-cells in the etiology of Hodgkin'sdisease and non-Hodgkin's lymphoma.

Methods

Two patients, each diagnosed with Hodgkin's disease and non-Hodgkin's lymphoma formed the basis of this study. Tumor cells, called Reed-Sternberg cells, which are the cancerous cells that cause Hodgkin's disease, were obtained from each patient. In addition, tumor cells were also obtained from non-Hodgkin's lymphoma tissue. Using polymerase chain reaction (PCR), the immunoglobulin genes of these tumor cells were amplified using primers from the V gene region of the B-cell. The PCR products were then sequenced and analyzed.

Results

In both patients, the Reed-Sternberg cell from the Hodgkin's disease and the cancer causing cell from the non-Hodgkin's lymphoma had nearly identical immunoglobulin genes. In addition, the V genes of the tumor cell carried somatic mutations, indicating that the tumor cells came from the area of lymphoid tissue where B-cells organize to fight infection (called the germinal center).

Conclusion

Examination of tumor cells in two separate patients each with Hodgkin's disease and non-Hodgkin's lymphoma revealed that the B-cell was found to be the common precursor in both patients and for each type of lymphoma. That is, in both patients, the Reed-Sternberg cells arose from B-cells, and each of their lymphomas arose from the same B-cell. These results provide compelling evidence of the role of the B-cell as a precursor to Hodgkin's disease and non-Hodgkin's lymphoma.