Clonal proliferation of B lymphocytes in the germinal centers of human reactive lymph nodes: Possibility of overdiagnosis of B cell clonal proliferation

Clonal expansion of the germinal center B cells of human reactive lymph nod es was analyzed. By micromanipulation, 28 germinal centers were microdissec ted from three nonneoplastic lymph nodes that had been fixed with formalin. Immunoglobulin heavy chain variable (V) region gene rearrangement was exam ined by seminested polymerase chain reaction (PCR) using two sets of primer s (FR2-J and FR3A-J). An oligoclonal development (one to five clones) was f ound in each germinal center. Depending on the primer used, four or five (1 6%) of the germinal centers showed a single rearrangement band. The average number of B-cell clones in each germinal center was approximately 2.5. Nex t, the authors analyzed 50 endoscopic biopsy specimens from 6 patients with non-mucosa-associated lymphoid tissue (MALT) type gastric lymphoma, 25 pat ients with chronic gastritis, and 19 patients with nonspecific colitis. In addition to the samples from the 6 patients with malignant lymphoma, 8 of 4 4 biopsy samples (18.2%) from patients diagnosed as having chronic gastriti s or nonspecific colitis showed one or two amplified bands. These results i ndicate that PCR analysis of immunoglobulin heavy chain V region gene rearr angement in small biopsy specimens could be misleading, causing overdiagnos is of reactive lymphoid tissue as B-cell clonal proliferation.