American Society of Hematology

Fig. 1.

$Fig. 1. Expression of BCL-6, MUM1, and CD138/syn-1 in reactive B cells identifies 3 major phenotypic patterns that correspond to physiologic stages of B-cell development. / A subset of germinal center B cells express MUM1 and are negative for CD138/syn-1 and BCL-6. (A) Serial sections from hyperplastic lymph node from an HIV-infected patient with persistent generalized lymphadenopathy (PGL). (Left) Within a follicle numerous germinal center (GC) cells (centroblasts and centrocytes) exhibit nuclear staining (red) for BCL-6, whereas B cells of the mantle and perifollicular areas score negative. (Center) In the same follicle, expression of MUM1 is restricted to a subset of cells located in the GC. Conversely, most MUM1+ cells are located in the perifollicular and interfollicular areas; brown staining is nuclear. (Right) In the same field, large cells with plasma cell morphology show strong cytoplasmic and membrane staining (red) with the anti–syn-1 mAb. They are present within the perifollicular and interfollicular areas in which MUM1+ cells are more numerous (compare figure on the right for syn-1 and figure in the center for MUM1). Conversely, syn-1 is absent in intrafollicular or extrafollicular cell populations other than plasma cells (see also panel B). Thus, the coordinated expression of BCL-6, MUM1, and syn-1 in reactive B cells shows 3 major phenotypic patterns corresponding to physiologic stages of B-cell differentiation—(1) centroblasts (the BCL-6+/MUM1−/syn-1− profile, identified by green squares; (2) late GC/early post-GC B cells (the BCL-6−/MUM1+/syn-1− profile, identified by white rectangles); (3) post-GC B cells (the BCL-6−/MUM1+/syn-1+ profile, identified by red rectangles). Paraffin-embedded tissue sections, APAAP (left and right), immunoperoxidase (center), hematoxylin counterstain. Original magnification, × 250. (B) With the exception of plasma cells, MUM1+ cells in the GC and in the perifollicular areas are negative for CD138/syn-1. Hyperplastic lymph node from an HIV-infected patient with PGL. Two-color staining. The figure shows a follicle with a large GC and a thin mantle zone. Numerous perifollicular cells and some scattered GC cells exhibit nuclear staining (red) for MUM1. Moreover, in the same field, a fraction of large cells exhibiting plasma cell morphology coexpresses syn-1 with a strong cytoplasmic and membrane staining (blue). Cells coexpressing MUM1 and syn-1 are numerous within the perifollicular zone but are rare within the GC. Paraffin-embedded tissue section, no counterstain. Original magnification, × 250. (C) Expression of MUM1 by GC B cells is mutually exclusive with the expression of BCL-6 by the same cell. Reactive tonsil from an HIV-infected patient with persistent generalized lymphadenopathy with 2-color staining. Within a follicle, numerous GC cells exhibit nuclear staining (red) for BCL-6. In the same GC, several cells show nuclear staining (brown) with the anti-MUM1 antibody. MUM1+ cells are also present around the GC. No coexpression of BCL-6 or MUM1 markers by the same GC cell is detectable. Paraffin-embedded tissue section, no counterstain. Original magnification, × 250.$

Expression of BCL-6, MUM1, and CD138/syn-1 in reactive B cells identifies 3 major phenotypic patterns that correspond to physiologic stages of B-cell development.

A subset of germinal center B cells express MUM1 and are negative for CD138/syn-1 and BCL-6. (A) Serial sections from hyperplastic lymph node from an HIV-infected patient with persistent generalized lymphadenopathy (PGL). (Left) Within a follicle numerous germinal center (GC) cells (centroblasts and centrocytes) exhibit nuclear staining (red) for BCL-6, whereas B cells of the mantle and perifollicular areas score negative. (Center) In the same follicle, expression of MUM1 is restricted to a subset of cells located in the GC. Conversely, most MUM1⁺ cells are located in the perifollicular and interfollicular areas; brown staining is nuclear. (Right) In the same field, large cells with plasma cell morphology show strong cytoplasmic and membrane staining (red) with the anti–syn-1 mAb. They are present within the perifollicular and interfollicular areas in which MUM1⁺ cells are more numerous (compare figure on the right for syn-1 and figure in the center for MUM1). Conversely, syn-1 is absent in intrafollicular or extrafollicular cell populations other than plasma cells (see also panel B). Thus, the coordinated expression of BCL-6, MUM1, and syn-1 in reactive B cells shows 3 major phenotypic patterns corresponding to physiologic stages of B-cell differentiation—(1) centroblasts (the BCL-6⁺/MUM1⁻/syn-1⁻ profile, identified by green squares; (2) late GC/early post-GC B cells (the BCL-6⁻/MUM1⁺/syn-1⁻ profile, identified by white rectangles); (3) post-GC B cells (the BCL-6⁻/MUM1⁺/syn-1⁺ profile, identified by red rectangles). Paraffin-embedded tissue sections, APAAP (left and right), immunoperoxidase (center), hematoxylin counterstain. Original magnification, × 250. (B) With the exception of plasma cells, MUM1⁺ cells in the GC and in the perifollicular areas are negative for CD138/syn-1. Hyperplastic lymph node from an HIV-infected patient with PGL. Two-color staining. The figure shows a follicle with a large GC and a thin mantle zone. Numerous perifollicular cells and some scattered GC cells exhibit nuclear staining (red) for MUM1. Moreover, in the same field, a fraction of large cells exhibiting plasma cell morphology coexpresses syn-1 with a strong cytoplasmic and membrane staining (blue). Cells coexpressing MUM1 and syn-1 are numerous within the perifollicular zone but are rare within the GC. Paraffin-embedded tissue section, no counterstain. Original magnification, × 250. (C) Expression of MUM1 by GC B cells is mutually exclusive with the expression of BCL-6 by the same cell. Reactive tonsil from an HIV-infected patient with persistent generalized lymphadenopathy with 2-color staining. Within a follicle, numerous GC cells exhibit nuclear staining (red) for BCL-6. In the same GC, several cells show nuclear staining (brown) with the anti-MUM1 antibody. MUM1⁺ cells are also present around the GC. No coexpression of BCL-6 or MUM1 markers by the same GC cell is detectable. Paraffin-embedded tissue section, no counterstain. Original magnification, × 250.

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