American Society of Hematology

Fig. 4.

$Fig. 4. A model of HD histogenesis. The proposed model is based on the expression pattern of BCL-6 and syn-1 throughout physiologic B-cell differentiation. B cells within the GC display the BCL-6+/syn-1− phenotype, whereas B cells that have exited the GC and have undergone further maturation toward the plasma cell stage exhibit the BCL-6−/syn-1+ phenotype. On this basis, neoplastic cells of NLPHD consistently express the BCL-6+/syn-1− phenotype and thus closely reflect the GC phenotype. Conversely, RS cells of CHD may express either the BCL-6+/syn-1− phenotype or the BCL-6−/syn-1+ phenotype, consistent with further maturation toward the late stages of B-cell differentiation. Most CHD cases display only BCL-6−/syn-1+RS cells, whereas a fraction of CHD displays a mixture of BCL-6+/syn-1− and BCL-6−/syn-1+ RS cells, suggesting heterogeneity in the differentiation stage of the neoplastic clone. The CD40 molecule is expressed on neoplastic cells of both NLPHD and HD, whereas expression of CD40L by reactive T cells is restricted to the case of CHD and is consistently absent in NLPHD. In CHD containing both BCL-6+/syn-1− and BCL-6−/syn-1+ RS cells, CD40L+ T cells preferentially cluster around BCL-6−/syn-1+ RS cells. This model suggests that CD40/CD40L-mediated interactions between tumor and reactive cells modulate the differentiation of the neoplastic clone and is consistent with the in vitro observation that CD40/CD40L interactions downregulate BCL-6 in B cells with a GC phenotype.$

A model of HD histogenesis. The proposed model is based on the expression pattern of BCL-6 and syn-1 throughout physiologic B-cell differentiation. B cells within the GC display the BCL-6⁺/syn-1⁻ phenotype, whereas B cells that have exited the GC and have undergone further maturation toward the plasma cell stage exhibit the BCL-6⁻/syn-1⁺ phenotype. On this basis, neoplastic cells of NLPHD consistently express the BCL-6⁺/syn-1⁻ phenotype and thus closely reflect the GC phenotype. Conversely, RS cells of CHD may express either the BCL-6⁺/syn-1⁻ phenotype or the BCL-6⁻/syn-1⁺ phenotype, consistent with further maturation toward the late stages of B-cell differentiation. Most CHD cases display only BCL-6⁻/syn-1⁺RS cells, whereas a fraction of CHD displays a mixture of BCL-6⁺/syn-1⁻ and BCL-6⁻/syn-1⁺ RS cells, suggesting heterogeneity in the differentiation stage of the neoplastic clone. The CD40 molecule is expressed on neoplastic cells of both NLPHD and HD, whereas expression of CD40L by reactive T cells is restricted to the case of CHD and is consistently absent in NLPHD. In CHD containing both BCL-6⁺/syn-1⁻ and BCL-6⁻/syn-1⁺ RS cells, CD40L⁺ T cells preferentially cluster around BCL-6⁻/syn-1⁺ RS cells. This model suggests that CD40/CD40L-mediated interactions between tumor and reactive cells modulate the differentiation of the neoplastic clone and is consistent with the in vitro observation that CD40/CD40L interactions downregulate BCL-6 in B cells with a GC phenotype.

This Feature Is Available To Subscribers Only