Immunoultrastructural and morphometric analysis of B lymphocytes in human germinal centers. Evidence for alternate pathways of follicular transformation.

Monoclonal antibodies to B-cell differentiation antigens B1, B2, C3b, and Ia were used for ultrastructural characterization of B lymphocytes undergoing follicular transformation in human germinal centers. Morphologic alterations and morphometric parameters including form factor (FF) and nuclear contour index (NCI) were evaluated. Antibodies to B1, Ia, and C3b revealed uninterrupted linear surface membrane staining in B cells at various stages of transformation, while staining for B2 appeared as aggregates of gold particles localized to sites of antigen expression along the cell membrane. B cells with highly irregular or convoluted nuclei (NCI greater than 6.5) formed 3% of follicular lymphocytes and may explain the derivation of rare follicular center cell lymphomas with marked nuclear irregularity which mimic T-cell lymphomas histologically. Cleaved cells (NCI greater than or equal to 4.5) comprised 48% of the cellular population and were present at all stages of transformation. Results of morphometric studies suggest that small cleaved cells (centrocytes) and noncleaved cells transform to large lymphoid cells (centroblasts) along parallel lines, and without following the sequential differentiation pathway suggested by Lukes and Collins.