Figure 1.

Relationship between p27Kip1 expression and B-cell differentiation stage as defined by BCL-6, MUM1, and syn-1 in nontransformed lymphoid tissues. Serial sections from hyperplastic lymph node from an HIV-infected individual with persistent generalized lymphadenopathy. A: A follicle with a large GC (left) and perifollicular/interfollicular areas (right) is shown. Numerous small lymphocytes in the follicular mantle zone exhibit nuclear staining (brown) for p27Kip1. Several plasma cells in the perifollicular areas (dotted area and inset) also score positive. p27Kip1 is absent in large blast cells in the perifollicular area (inset, arrows). B: Within the same follicle, numerous GC cells (centroblasts and centrocytes) exhibit nuclear staining (brown) for BCL-6, whereas B cells in the mantle zone and perifollicular/interfollicular areas score negative (see also dotted area and inset). C: Expression of MUM1 is restricted to a small subset of cells located in the GC and to a group of perifollicular plasma cells (dotted area and inset); the staining is nuclear (brown). D: In the same field, cells with a plasma cell morphology show a strong cytoplasmic and membrane staining (red) with the anti-syn-1 mAb. They are present within the perifollicular areas (dotted area and inset). Conversely, intrafollicular or extrafollicular cell populations other than plasma cells are devoid of syn-1 staining. Thus, the coordinated expression of BCL-6, MUM1, and syn-1 in reactive B cells shows that the expression of p27Kip1 occurs early before B-cell entry in the GC, because it is found in mantle zone B cells but not in GC B cells. During the phases of B-cell transit through the GC, B cells undergo a decrease in p27Kip1 expression, switch off BCL-6, and start to express MUM1. Finally, on GC exit and differentiation to plasma cells, B cells express p27Kip1 and syn-1. Paraffin-embedded tissue sections, immunoperoxidase method (A–C), alkaline phosphatase anti-alkaline phosphatase method (D), hematoxylin counterstain. Original magnifications, ×250.